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Bioactive peptides from marine sources: Pharmacological properties and isolation procedures
Abstract
Marine organisms represent a valuable source of new compounds. The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new active substances in the field of the development of bioactive products. In this paper, the molecular diversity of different marine peptides is described as well as information about their biological properties and mechanisms of action is provided. Moreover, a short review about isolation procedures of selected bioactive marine peptides is offered. Novel peptides from sponges, ascidians, mollusks, sea anemones and seaweeds are presented in association with their pharmacological properties and obtainment methods.
... The most abundant amino acids present in seaweed protein are glycine, proline, aspartic acid, glutamic acid, alanine, and arginine with threonine, lysine, tryptophan, cysteine, methionine, and histidine being less abundant ( Cerná, 2011;Marinho et al., 2015). In addition to the 20 DNA-coded amino acids, seaweeds can contain unusual amino acids that are not often present in terrestrial plants, such as aminobutyric acid, ornithine, citrulline, hydroxyproline, phycobiliproteins, and mycosporinelike amino acids (Aneiros and Garateix, 2004;Dawczynski et al., 2007;De la Coba et al., 2009;Fitzgerald et al., 2011). Other amino acid-like compounds such as chondrine, gigartine, baikiain, rhodoic acid, domoic acid, kainic acid, taurine, and laminine are also found in seaweeds (Aneiros and Garateix, 2004;Fitzgerald et al., 2011). ...
... In addition to the 20 DNA-coded amino acids, seaweeds can contain unusual amino acids that are not often present in terrestrial plants, such as aminobutyric acid, ornithine, citrulline, hydroxyproline, phycobiliproteins, and mycosporinelike amino acids (Aneiros and Garateix, 2004;Dawczynski et al., 2007;De la Coba et al., 2009;Fitzgerald et al., 2011). Other amino acid-like compounds such as chondrine, gigartine, baikiain, rhodoic acid, domoic acid, kainic acid, taurine, and laminine are also found in seaweeds (Aneiros and Garateix, 2004;Fitzgerald et al., 2011). Seaweeds also contain peptides, commonly between 2 and 20 amino acid residues in length, that are released by autolysis or hydrolysis from parent peptides and proteins, some of which mimic hormones or exhibit druglike activities and influence physiological functions by inhibiting enzymes or by binding cell receptors (Cermeño et al., 2019;Erdmann et al., 2008;Fitzgerald and Murray, 2006;Garcia-vaquero et al., 2019). ...
... Seaweeds also contain peptides, commonly between 2 and 20 amino acid residues in length, that are released by autolysis or hydrolysis from parent peptides and proteins, some of which mimic hormones or exhibit druglike activities and influence physiological functions by inhibiting enzymes or by binding cell receptors (Cermeño et al., 2019;Erdmann et al., 2008;Fitzgerald and Murray, 2006;Garcia-vaquero et al., 2019). Seaweed proteins have also been shown to exhibit several therapeutic functions like mineral binding and immunomodulation, as well as antimicrobial, antioxidant, antithrombotic, antihypertension, and hypocholesterolaemia activity (Aneiros and Garateix, 2004;Cornish and Garbary, 2010;De la Coba et al., 2009;Erdmann et al., 2008;Fitzgerald et al., 2011;Garcia-Vaquero et al., 2019;Tierney et al., 2010). ...
Seaweeds, particularly algae, are rich sources of biochemicals including proteins, carbohydrates, fatty acids, and phytochemicals such as carotenoids, polyphenols, and flavonoids. These chemicals play essential roles in human well-being and are present in significant quantities in seaweed. Seaweeds, as primary producers, are capable of sequestering minerals and nutrients from seawater, which serve as precursors for the biosynthesis of complex biomolecules. The diverse chemical profile of seaweeds is likely a result of their unique and challenging environmental niche. This book chapter summarises some of the important chemicals produced by seaweeds that are relevant to human nutrition.
... However, there are many freshwater fish species found in Thailand, such as Oreochromis niloticus (plaa-nile), Catla catla (plaa-ka-ho), Labeo rohita (plaa-yi-sok), Cirrhinus mrigala (plaa-nuan-chan), Cyprinus carpio (plaa-nai), Pangasianodon hypophthalmus (plaa-sa-way), and Barbonymus gonionotus (plaa-ta-pien), that do not deliver their full nutritional potential upon direct human consumption. Proteolytic pre-treatments are required to obtain their full nutritional benefits [2]. ...
... Biologically active hydrolysates can be promoted as food additives providing a value-added type of product, a so-called functional food [8,10]. Particularly, bioactive peptides refer to short peptide sequences of approximately 2 to 30 amino acids that are enzymatically released from polypeptides or protein from any source [2,[7][8][9]. These so-called bioactive peptides are specific peptide fragments that exhibit a constructive function in providing a beneficial influence upon health after consumption [8,9]. ...
... Treatment of both FS-trypsin and FF-trypsin exhibited the highest reducing power, 197.0 and 196.3 µmoL TE/g PH, after 120 min incubation, respectively. Numerous studies have found that there is a correlation between antioxidant scavenging activities and reducing power of certain bioactive molecules [2,8,10]. Similarly, previous studies [27,28] also reported that the highest hydrolysis degree for fish protein hydrolysates of Catla catla and Cyprinus carpio were achieved after 120 min. ...
The antioxidant effects of silver BARB (Barbonymus gonionotus) protein hydrolysates (SBPHs) were investigated under various trypsin and protease treatments. Biochemical characterization and antioxidant activities of 5% (w/v) SBPHs were examined from both fresh fish (FF) and saline-soaked fish (SF) proteins. The
highest levels of trichloroacetic acid (TCA)-soluble peptide contents, 57.7 and 58.6 mg/g BARB hydrolysate (BH), were obtained from FF-trypsin and SF-trypsin, respectively, while the highest levels of free amino nitrogen (FAN) contents, 1.9 and 1.8 µmoL tyrosine/g BH, were respectively found after incubation for 150 min. Additionally, these treatments degraded large proteins into small molecular weights sizes of less than 10.5 kDa after 60 to 150 min of incubation. The highest percentage of 2,2 diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging inhibition of FF-trypsin, 38%, was obtained after 120 min of incubation. Similarly, the highest ferric reducing antioxidant power (FRAP) capacities for both SF-trypsin and FF-trypsin were, respectively, 186.3 and
185.4 µmoL TE/g BH after 120 min of incubation. Furthermore, SF-trypsin exhibited the highest 2,2'-azino-bis-3 ethylbenzothiazoline-6-sulfonic acid (ABTS) radical-scavenging inhibition, 91.0%, after 90 min of incubation. These results suggest that the by-products of SBPHs obtained from trypsin, especially natural antioxidant compounds, may be useful for consumer health if used in functional foods.
... Marine organisms have been considered to be a promising source of numerous nutraceutical and pharmaceutical compounds [33,34]. Over the last few decades, new marine-derived compounds have been considered not only as lead compounds for drug discovery, but also as bioactive agents in pharmaceutical research, possessing antifungal, antibacterial, cytotoxic and anti-inflammatory properties, among others [35][36][37][38]. ...
... Specific chemical and physical properties, such as water salt concentrations, pressure, temperature (including extreme), light penetration, ocean currents, oxygen concentrations, and radiation exposure characterize different underwater habitats (environment) of marine organisms [39,40]. Due to this extreme environment, marine organisms are forced to produce a chemical diversity of bioactive compounds that are considered essential for the discovery and development of new agents for the treatment and prevention of various fungal, bacterial, viral, and protozoal infections [36,[41][42][43][44][45][46]. ...
... Marine organisms have been considered to be a promising source of numerous nutraceutical and pharmaceutical compounds [32,33]. Over the last few decades, new marine-derived compounds have been considered not only as lead compounds for drug discovery, but also as bioactive agents in pharmaceutical research, possessing antifungal, antibacterial, cytotoxic and anti-inflammatory properties, among others [34][35][36][37]. ...
Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a broad spectrum of antimicrobial activities, including against bacteria, protozoa, fungi, and viruses. Moreover, there are several examples of marine cyclic peptides revealing interesting antimicrobial activities against numerous drug-resistant bacteria and fungi, making these compounds a very promising resource in the search for novel antimicrobial agents to revert multidrug-resistance. This review summarizes 174 marine cyclic peptides with antibacterial, antifungal, antiparasitic, or antiviral properties. These natural products were categorized according to their sources—sponges, mollusks, crustaceans, crabs, marine bacteria, and fungi—and chemical structure—cyclic peptides and depsipeptides. The antimicrobial activities, including against drug-resistant microorganisms, unusual structural characteristics, and hits more advanced in (pre)clinical studies, are highlighted. Nocathiacins I–III (91–93), unnarmicins A (114) and C (115), sclerotides A (160) and B (161), and plitidepsin (174) can be highlighted considering not only their high antimicrobial potency in vitro, but also for their promising in vivo results. Marine cyclic peptides are also interesting models for molecular modifications and/or total synthesis to obtain more potent compounds, with improved properties and in higher quantity. Solid-phase Fmoc- and Boc-protection chemistry is the major synthetic strategy to obtain marine cyclic peptides with antimicrobial properties, and key examples are presented guiding microbiologist and medicinal chemists to the discovery of new antimicrobial drug candidates from marine sources.
... In recent years, active biomolecules that derived from marine resources are highly recommended in therapeutics due to their fewer side effects and more bioavailability (Wijesekara et al., 2011). Algae are highly diverse group of aquatic plants that produce various bioactive compounds due to exposure to a wide range of environmental variables (Aneiros and Garateix, 2004). Some bioactive compounds that isolated from algae, can be used as valuable inducers for bone formation after evaluation in animal models. ...
... Phycobiliproteins are spontaneously fluorescent molecules and this property is specially used in biotechnological applications. so, they are used in a wide variety of biomedical diagnostic systems mainly in immunochemical methods (Aneiros and Garateix, 2004), especially, PE pigment is used as a probe in medical and biological analyzes due to its fluorescent properties (Thoisen et al., 2017). Although some research approved bone resorption inhibition with phycobiliproteins but there is rare information about their effects on osteogenesis. ...
... Certain studies highlight the unique secondary metabolites in seaweeds, which exhibit a broad range of biological activities, including antibacterial, anti-inflammatory, anticancer, antidiabetic, and anti-HIV properties (Imran et al. 2023;Otero et al. 2023;Wang et al. 2009Wang et al. , 2010. Given the rising threat of antibiotic-resistant infections, seaweeds are a promising source of novel antimicrobial agents with potential therapeutic applications (Aneiros and Garateix 2004). ...
The present study elucidates the bioactive metabolites, antioxidants, and antibacterial potential of selected seaweeds – Kappaphycus alvarezii , Caulerpa chemnitzia , and Sargassum tenerrimum – collected from the southwest coast of India. Biomolecules were extracted using six solvents: hexane, dichloromethane, ethyl acetate, acetone, methanol, and ethanol. Among these, ethanol proved to be the most efficient extraction solvent. Notably, the ethanolic extract of S . tenerrimum exhibited high phenolic and flavonoid contents, contributing to its potent antioxidant and antibacterial properties. In contrast, the extracts of C . chemnitzia were rich in tannins, demonstrating marked antioxidant activity. Gas Chromatography-Mass Spectrometry profiling identified approximately 42 bioactive compounds with antimicrobial, antioxidant, anticancer, antidiabetic, and cardioprotective properties. Key compounds included stigmasta-5, 24(28)-dien-3-ol (3β, 24Z), cholesterol margarate, arachidonic acid, squalene, 1-hexadecanol, and δ-tocopherol, all of which hold significant nutraceutical and cosmetic value. Furthermore, antibacterial susceptibility tests against nine bacterial strains revealed that K . alvarezii was particularly effective against gram-positive bacteria, while the C . chemnitzia and S . tenerrimum extracts showed considerable efficacy against both gram-negative and gram-positive bacterial strains.
... Apart from this, two bioactive proteins such as Lectins and phycobiliproteins, have been strategically utilized for several industrial applications. Lectins a well-known glycoproteins used by various biotechnological industries as cancer biomarkers, blood grouping, cell-cell communication, Likewise, phycobiliproteins are used in fluorescent labelling, flow cytometry, fluorescent microscopy, and fluorescent immunohistochemistry [73,74]. The elemental composition of MAFP, microalgae, and microalgal biomass is presented in Table 3. ...
Hydroponic effluent (HE), enriched with inorganic nutrients, presents a viable, low-cost cultivation medium for microalgal biomass production and subsequent resource recovery. However, downstream processing, particularly biomass harvesting, remains a critical challenge for micro-algal biorefineries. Therefore, the present study explored the potential of microalgal-fungal pellets (MAFP) in HE recycling for the production of biochemical-rich biomass. The optimized fungi-to-microalgae ratio (F:A) of 1:3 resulted in 100 % microalgal pelletization within 6 h. Surface characteristics suggested that metabolically active fungi with opposite charges facilitate micro-algal pelletization. Further, MAFP exhibited a packed porous structure that was resilient to shear forces and had a high capacity for nutrient uptake. MAFP cultivation in HE demonstrated complete removal of ammonia-nitrogen (NH₃-N), phosphate (PO₄ 3 ⁻), and nitrate-nitrogen (NO₃⁻-N) within 7-9 days. The produced biomass was rich in biomolecules, including lipids (18.36 ± 0.12 % TS), protein (52.06 ± 2.1 % TS), and carbohydrates (28.95 ± 0.05 % TS). Besides, the high methane potential of MAFP (SMP ≈ 502.74 ± 19.1 mL CH 4 g − 1 VS, and TMP ≈ 817.68 ± 12.5 mL CH 4 g − 1 VS) indicated its suitability for biogas production. In essence, MAFP offers efficient HE recycling and biochemically rich biomass production, advancing towards a green and circular bioeconomy.
... For many years, sponges have been recognized for providing novel bioactive metabolites, including, polyethers, macrolides terpenoids, nucleoside derivatives, alkaloids, and many other chemical substances. An anticancer substance Cytosine Arabinoside, was subsequently create the synthetic analogues of the Cnucleosides pongouridine and pongothymidine that were discovered from a Caribbean sponge (Aneiros, and Garateix, 2004). Photosynthetic microorganisms called marine cyanobacteria are widely found in nature (Silipo, et al,. ...
Bioactive peptides from marine species have gained attention due to their promising biological features, and the disciplines of pharmaceutical, cosmeceutical, nutraceutical, and biomedical product development have increased recently. Their molecular mass, immunity, and natural abilities that they evolved are essential for host defense mechanisms. Marine bioactive peptides have extremely complex and diverse structures that vary greatly depending on the sources from which they are obtained. They frequently have secondary structures and can be cyclic in the form of depsi-peptides. Bioactive peptide purification from marine sources can be achieved via chromatography techniques, including reverse-phase high-performance liquid chromatography, gel filtration chromatography, and ion exchange chromatography, which is a current technique to extract biologically active peptides. Studies of marine plants, microbes, and animals over the last several eras have revealed a huge variety of structurally varied and bioactive secondary metabolites. With a particular focus on the conversion of nutraceutical and pharmaceutical research into commercially available products, this review summarizes current findings in marine peptide research as well as emerging patterns, and its promising directions are briefly reviewed. The use of active peptides derived from the sources mentioned earlier their health advantages and bioactivities are also focused. Along with safety concerns, their possible usages in the processed food industry, wound healing, feed, cosmetic, and pharmaceutical industries, for the growth of efficient goods, are highlighted.
... Recently, the bioactive peptides, including an antioxidant, anti-inflammatory, antimicrobial and antihypertension, from seaweed hydrolysate were widely investigated [6,7]. The peptides from the protein of macroalage have a potential application to improve health benefit and to treat disease [8][9][10][11]. The peptides from Ulva spp. were supposed to have the bioactivity, including the inhibition of angiotensin-I converting enzyme (ACE), dipeptidyl peptidase IV, dipeptidyl peptidase III, renin and α-glucosidase. ...
The protein extract of Ulva australis hydrolyzed with alcalase and flavourzyme investigated multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of U. australis hydrolysate from cation-exchange chromatography showed significantly high TAC, collagenase inhibitory and antibacterial effects against Propionibacterium acnes, and only Q3 fraction from anion-exchange chromatography showed high multi-functional activities. The eight peptides among 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results to screen molecular docking on target proteins, and were synthesized. Thr-Gly-Thr-Trp (TGTW) showed ABTS [2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. Effect TAC as Trolox equivalence was dependent on the concentration of TGTW. The Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) possessing collagenase inhibitory activity increased according to the increase of concentration and the IC50 values of them were 0.95 mM and 0.84 mM, respectively. Peptides, RDRF and His-Ala-Val-Tyr (HAVY) showed anti-P. acnes effects with IC50 values of 8.57 mM and 13.23 mM, respectively. These results suggest that the U. australis hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics.
... (b) Phycobiliproteins: Red algae can contain considerable amount of phycobiliproteins, particularly phycoerythrin, with values of 1.2% (total dw) observed for P. palmatum (Wang et al. 2001). Fluorescence labelling, flow cytometry, fluorescent microscopy, and fluorescent immunohistochemistry technique could be employed using phycobiliproteins (Aneiros and Garateix 2004). Phycocyanin, a phycobiliprotein, a blue pigment used in chewing gum, popsicles, confectionery, soft drinks, dairy products, and wasabi, as well as in cosmetics like lipstick and eyeliner (Spolaore et al. 2006). ...
Covers recent topics of algae from bionanopesticides to genetic engineering
Presents algal biotechnology, updated food processing techniques and Biochemistry of Haematococcus
Offers information on the less explored areas of in silico therapeutic and clinical applications
... Recently, bioactive peptides from hydrolysate of seaweed, including antioxidant, anti-inflammatory, antimicrobial, and antihypertension, were widely investigated [6,7]. The peptides from the protein of macroalgae have potential applications to provide health benefits and treat disease [8][9][10][11]. The peptides from Ulva spp. were supposed to exhibit bioactivity, including the inhibition of angiotensin-I-converting enzyme (ACE), dipeptidyl peptidase IV, dipeptidyl peptidase III, renin, and α-glucosidase. 1 The powder of dried samples was hydrolyzed by 6 HCl, and analyzed with sodium buffer system in amino acid analyzer. ...
The protein extract of Ulva australis hydrolyzed with Alcalase and Flavourzyme was found to have multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory, and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of U. australis hydrolysate from cation-exchange chromatography displayed significantly high TAC, collagenase inhibitory, and antibacterial effects against Propionibacterium acnes, and only the Q3 fraction from anion-exchange chromatography displayed high multi-functional activities. Eight of 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results for screening with molecular docking on target proteins and were then synthesized. Thr-Gly-Thr-Trp (TGTW) displayed ABTS [2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. The effect of TAC as Trolox equivalence was dependent on the concentration of TGTW. Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) exhibited collagenase inhibitory activity, which increased according to the increase in concentration, and their IC50 values were 0.95 mM and 0.84 mM, respectively. Peptides RDRF and His-Ala-Val-Tyr (HAVY) displayed anti-P. Acnes effects, with IC50 values of 8.57 mM and 13.23 mM, respectively. These results suggest that the U. australis hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics.
... (b) Phycobiliproteins: Red algae can contain considerable amount of phycobiliproteins, particularly phycoerythrin, with values of 1.2% (total dw) observed for P. palmatum (Wang et al. 2001). Fluorescence labelling, flow cytometry, fluorescent microscopy, and fluorescent immunohistochemistry technique could be employed using phycobiliproteins (Aneiros and Garateix 2004). Phycocyanin, a phycobiliprotein, a blue pigment used in chewing gum, popsicles, confectionery, soft drinks, dairy products, and wasabi, as well as in cosmetics like lipstick and eyeliner (Spolaore et al. 2006). ...
Haematococcus is a genus of green microalgae widely distributed in freshwater and seawater and well known for their ability to produce astaxanthin, a powerful antioxidant with diverse applications. Eight species have been assigned to this genus based on a recent genetic classification and among them Haematococcus lacustris (previously named Haematococcus pluvialis) is the most studied. This species is regarded as the most promising microalgae for the production of natural astaxanthin. It is also known for its ability to synthesize other interesting bioactive compounds with a wide range of biological activities. The present work highlights the diverse therapeutic applications of Haematococcus bioactive molecules such as antioxidant, anti-inflammation, antimicrobial, skin protection, treatment and prevention of cancer, treatment of eye and neurodegenerative diseases, and immune stimulation.KeywordsAstaxanthinAntioxidantAnti-inflammationCancer preventionNeurodegenerative diseases
... From the investigations carried in the preceding years, it is foreseen that the bioactive compounds derived from oceanic source outperform to a great extent in terms of the structural diversity and uniqueness compared to ones that have been derived from terrestrial origin. In view of the remarkable biological functionality offered by the marine-derived bioactive compounds, they are undoubtedly regarded as important molecules in the formulation of novel and desirable agents in the fields of biomedicine and pharmaceutics (Aneiros & Garateix, 2004). Microorganisms residing at extreme habitats generate antibiotics posing enormous inhibitory actions against detrimental Gram +ve and Gram -ve bacteria (Fenical, 1993). ...
... From the investigations carried in the preceding years, it is foreseen that the bioactive compounds derived from oceanic source outperform to a great extent in terms of the structural diversity and uniqueness compared to ones that have been derived from terrestrial origin. In view of the remarkable biological functionality offered by the marine-derived bioactive compounds, they are undoubtedly regarded as important molecules in the formulation of novel and desirable agents in the fields of biomedicine and pharmaceutics (Aneiros & Garateix, 2004). Microorganisms residing at extreme habitats generate antibiotics posing enormous inhibitory actions against detrimental Gram +ve and Gram -ve bacteria (Fenical, 1993). ...
... MOA: Microspinosamide inhibited the cytopathic effect of HIV-1 infection in an XTT-based in vitro assay [73,74]. ...
... In addition to mechanical protection, the mucus of many cnidarians contains specific compounds to make the animal venomous, unpleasant, irritating or a combination of these characteristics. It is not surprising that these invertebrates have developed an innate immune system that produces a considerable number of defense molecules, such as lytic compounds (Mayer et al., 2013), bioactive antimicrobials (Aneiros and Garateix, 2004;Otero Gonzalez et al., 2010;Smith et al., 2010), toxins, and carbohydrate-based anti-adhesives (Bavington et al., 2004). ...
Mucus secretion provides an interface with unique and multifunctional properties between the epithelial cells of many aquatic organisms and their surrounding environment. Indeed, mucus is involved in various essential biological processes including feeding, reproduction, osmoregulation, competition for space, defense against pathogens, xenobiotics, and a multitude of environmental stressors. The ability to produce a functional mucus layer is an important evolutionary step, arising first in Cnidaria that allowed for the development of the mucus-lined digestive cavity seen in higher metazoans. Mucus secretion by cnidarians has been moderately investigated in both corals and jellyfish, which among cnidarians are the ones that have shown the highest secretion rates to date. However, although in corals the production of mucus has received more attention, especially in view of the important ecological role played in coral reefs, in medusozoans the topic is little considered. Although the mucus secreted by corals has innumerable and important immunological, nutritional, and protective responsibilities, it should be remembered that jellyfish too represent a fundamental component of marine trophic web, playing numerous and important roles that are still unclear today. What is certain is that jellyfish are characterized (especially in the era of climate change) by large fluctuations in population density, the ecological implications of which are poorly understood. However, in both cases (Medusozoans and Anthozoans) to date some aspects relating to mucous secretions seem completely obscure, such as the microbiome and its variations as a function of environmental conditions or ontogenetic development, its implications in the field of immunological ecology, the consequent energy costs and finally the role played by the mucus in evolutionary terms. This review summarizes the properties, functions, ecological implications and evolutionary importance of mucus, in cnidarians, mainly focusing its roles in corals and jellyfish. Understanding these aspects relating to the ecological and evolutionary importance played by mucus is of fundamental importance for the ecosystems functioning.
... Polypeptides from marine organisms have some unique structures and functions compared to those from terrestrial organisms and they have become the hotspot in the fields of new drug development and functional food research. Many marine polypeptides have physiological activities of anti-tumor, anti-oxidation, anti-fungus, anti-virus and immune regulation (Ngo et al., 2012;Rameshkumar et al., 2009;Aneiros and Garateix, 2004). Polypeptide from Chlamys farreri (PCF) is one of the marine bioactive peptides. ...
... Several marine sources were described, including marine-derived bacteria, cyanobacteria, marine sponges, and marine-derived fungi, among others. The potential of marine-derived cyclic peptides 1-91 as anticancer and antimicrobial agents is expected based on previous reviews [145][146][147], which reinforces the marine organisms as a rich source of bioactive compounds for these therapeutic classes. Nobilamide I In this section, the marine-derived cyclopeptides are organized according to the main biological activity. ...
Cyclopeptides are considered as one of the most important classes of compounds derived from marine sources, due to their structural diversity and a myriad of their biological and pharmacological activities. Since marine-derived cyclopeptides consist of different amino acids, many of which are non-proteinogenic, they possess various stereogenic centers. In this respect, the structure elucidation of new molecular scaffolds obtained from natural sources, including marine-derived cyclopeptides, can become a very challenging task. The determination of the absolute configurations of the amino acid residues is accomplished, in most cases, by performing acidic hydrolysis, followed by analyses by liquid chromatography (LC). In a continuation with the authors’ previous publication, and to analyze the current trends, the present review covers recently published works (from January 2018 to November 2022) regarding new cyclopeptides from marine organisms, with a special focus on their biological/pharmacological activities and the absolute stereochemical assignment of the amino acid residues. Ninety-one unreported marine-derived cyclopeptides were identified during this period, most of which displayed anticancer or antimicrobial activities. Marfey’s method, which involves LC, was found to be the most frequently used for this purpose.
... In compounds extracted from marine origins, bioactive properties with various activities have been observed, such as anti-tumour, anticancer, anti-microtubule, anti-proliferative, anti-hypertensive, cytotoxic, and antibiotic properties. These substances have a variety of chemical properties, including phenol, alkaloids, terpenoids, polyesters, and other secondary metabolites present in sponges, bacteria, dinoflagellate, and seaweed [6][7][8]. ...
Introduction:
Melanoma is known as an aggressive and highly lethal cancer. The poor prognosis and resistance to treatment are characteristics of melanoma. In melanoma cells, apoptosis signaling which relies heavily on the acute activity of mitochondria and reactive oxygen species (ROS) formation is suppressed. Studies have shown that compounds isolated from marine herbs and animals, have been shown to have cytotoxic consequences on cancerous cells in prior research. This study was designed to evaluate the apoptotic effect of methanolic extract of Persian Gulf shell-less marine mollusk (Peronia peronii) on skin mitochondria isolated from animal model of melanoma.
Purpose:
melanoma mitochondria obtained from skin of melanoma animal model are studied in this research to see whether extracts from Persian Gulf shell-less marine mollusk (Peronia peronii), has a cytotoxic impact on them.
Material and method:
In this study, the mitochondria were isolated from melanoma cells via differential centrifugation were treated with various concentrations (650, 1300 and 2600 µg/ml) of methanolic extract of Peronia peronii. Then MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) viability assay, Reactive oxygen species (ROS) determination, Mitochondrial Membrane Potential(MMP) decline assay, mitochondrial swelling and cytochrome c release determination were performed. Flow cytometry assay of % apoptotic vs necrotic phenotypes was also performed on extract treated melanoma cells.
Results:
The results of MTT assay showed that different concentrations of Peronia peronii extract significantly (P < 0.05) decreased the SDH activity in cancerous skin mitochondria with the IC50(1300 μg/ml). The ROS results also showed that all concentrations of Peronia peronii extracts significantly increased ROS production, MMP decline and the release of cytochrome c in cancer groups mitochondria. The swelling of mitochondria was significantly increased compared to the control group. In addition, the results of apoptosis assay showed that addition of root extract of Peronia peronii on melanoma cells increased apoptosis, while it had no effect on control non tumor cells.
Discussion and conclusion:
Based on these results, the presence of potentially bioactive compounds in Peronia peronii make this Persian Gulf coastal herb a strong candidate for further molecular studies and clinical research in the field of melanoma cancer therapy.
... Marine organisms including macro-and microalgae, fungi, bacteria, molluscs, and invertebrates are prolific sources of various compounds, which are continuously garnering attention for their strong bioactivity and unique chemical structures [16]. Sponges are invertebrates and belong to the phylum Porifera; they occur in the deep sea, in intertidal waters, as well as in fresh water bodies and are one of the leading sources of many pharmacologically active compounds [2]. Sponges lack nervous systems and do not respond to environmental changes, but they protect themselves with the use of their highly developed defence system that produces poisonous toxins and deterrent secondary metabolites to protect them from predators, competitors, and pathogens [20]. ...
Fractionated compounds and methanol extract of the sponge Haliclona cratera (Schmidt, 1862) were investigated for their antioxidant and anti-inflammatory activities. The extract was also analyzed for its cytotoxicity in RAW macrophages by MTT assay. Enzyme-linked immunosorbent assay was performed to check the inflammatory mediators' levels (TNF-α, COX-2, IL-1β, PGE2, IL-6). High-performance liquid chromatography-mass spectrometry was used for characterization of fractionated compounds. The extracts showed good bovine serum albumin denaturation inhibition and poor antioxidant activity. It was also observed that the sponge extract did not show good cell viability which indicated its cytotoxic nature. Hc_EA_2, Hc_CHCl 3 _7, Hc_EA_5, and Hc_CHCl 3 _6 showed best IL-1β and IL-6 inhibition in the range of 14.10-61.91%. Hc_EA_2, Hc_EA_5, Hc_CHCl 3 _7 and Hc_CHCl 3 _6 inhibited TNF-α levels at 74.78, 80.45, 74.16 and 81.29%, respectively. Fractionated compounds reduced the levels of IL-1β, IL-6, PGE2, TNF-α and NO considerably in rats subjected to carrageenan-induced inflammation. Three compounds were characterized as per MS data, namely Sphingosine with isopropyl terminus, 24-methyl-5~-cholesta-7,9(11),24(28) ~-trien-38-o1 and 24-vinyl-cholest-9-ene-3β, 24-diol.
... Los moluscos se han cultivado para autoconsumo durante mucho tiempo; los registros más antiguos provienen del imperio romano y de la antigua Grecia, de los que existen evidencias de cultivos de ostras. Los gasterópodos, bivalvos, poliplacóforos y cefalópodos incluyen un gran número de especies de importancia comercial; su carne se utiliza como alimento, y en la industria son fuente de productos farmacéuticos (Aneiros y Garateix 2004, Blunt et al. 2008, Benkendorff 2010. ...
... Los moluscos se han cultivado para autoconsumo durante mucho tiempo; los registros más antiguos provienen del imperio romano y de la antigua Grecia, de los que existen evidencias de cultivos de ostras. Los gasterópodos, bivalvos, poliplacóforos y cefalópodos incluyen un gran número de especies de importancia comercial; su carne se utiliza como alimento, y en la industria son fuente de productos farmacéuticos (Aneiros y Garateix 2004, Blunt et al. 2008, Benkendorff 2010. ...
El capítulo compila toda la información sobre la diversidad de moluscos marinos en Oaxaca. Se describe brevemente la riqueza de especies, su distribución, importancia
ecológica, económica y/o cultural, las amenazas y propuestas para favorecer la conservación de los moluscos.
... Los moluscos se han cultivado para autoconsumo durante mucho tiempo; los registros más antiguos provienen del imperio romano y de la antigua Grecia, de los que existen evidencias de cultivos de ostras. Los gasterópodos, bivalvos, poliplacóforos y cefalópodos incluyen un gran número de especies de importancia comercial; su carne se utiliza como alimento, y en la industria son fuente de productos farmacéuticos (Aneiros y Garateix 2004, Blunt et al. 2008, Benkendorff 2010. ...
Después de los artrópodos, los moluscos son el grupo animal más exitoso en términos del número de especies y por la gran variedad de hábitats que ocupan, tanto acuáticos
como terrestres. Aunque la mayoría son marinos y de latitudes tropicales, se les encuentra desde los mares árticos, ríos, lagunas, lagos, esteros, pequeños arroyos, en los valles y laderas de las montañas, desde los 7 000 m de profundidad oceánica hasta los 3 000 m sobre el nivel del mar (Brusca et al. 2016).
... Marine organisms are considered as a rich source of bioactive peptides and natural small molecules; they account for half of the total global biodiversity. 1 As the most ancient venomous lineage, the phylum Cnidaria, which appeared approximately 600 million years ago, encompasses more than 13 000 species. In general, the cnidarians can be categorized into five classes: Hydrozoa (hydra); Scyphozoa (jellyfishes); Cubozoa (sea wasps); Staurozoa (sessile medusae); and Anthozoa (corals, sea anemones, zoanthids, etc.). 2 Interestingly, in contrast with other venomous phyla, cnidarians produce venom throughout the whole organism rather than in a single or limited number of discrete anatomical structures. ...
Neuropeptides are a group of neuronal signaling molecules that regulate physiological and behavioral processes in animals. Here, we used in silico mining to predict the polypeptide composition of available transcriptomic data of Turbinaria peltata. In total, 118 transcripts encoding putative peptide precursors were discovered. One neuropeptide Y/F-like peptide, named TpNPY, was identified and selected for in silico structural, in silico binding, and pharmacological studies. In our study, the anti-inflammation effect of TpNPY was evaluated using an LPS-stimulated C8-D1A astrocyte cell model. Our results demonstrated that TpNPY, at 0.75-3 μM, inhibited LPS-induced NO production and reduced the expression of iNOS in a dose-dependent manner. Furthermore, TpNPY reduced the secretion of proinflammatory cytokines. Additionally, treatment with TpNPY reduced LPS-mediated elevation of ROS production and the intracellular calcium concentration. Further investigation revealed that TpNPY downregulated the IKK/IκB/NF-κB signaling pathway and inhibited expression of the NLRP3 inflammasome. Through molecular docking and using an NPY receptor antagonist, TpNPY was shown to have the ability to interact with the NPY Y1 receptor. On the basis of these findings, we concluded that TpNPY might prevent LPS-induced injury in astrocytes through activation of the NPY-Y1R.
... Researchers are mainly focusing on marine natural products to produce new powerful and potential drugs including anti-HIV, anti-cancer, anti-microbials, and Alzheimer's therapeutics. Most of the bioactive compounds are organic compounds obtained from nature such as proteins, enzymes, large polymers, fatty acids, peptides, etc. Cyclic and linear peptides play a pivotal role in pharmaceutical development (Aneiros and Garateix 2004). Novel peptides from marine resources are become a new alternative for biomedical research due to their broad spectrum of activities. ...
Lectins are a class of specific carbohydrate binding proteins that can agglutinate cells or precipitate polysaccharides and glycoproteins and function as recognition molecules. They vary in molecular size, amino acid composition, three-dimensional structure, metal requirement, and function in order to adapt to the challenges of the antigens/ pathogens in the surrounding environment. There are different types of lectins such as C-type (calcium dependent lectin), S-type or Galectins (β-galactoside binding lectins), L-type (lectins containing leguminous lectin domain), MBL (mannose-binding lectin), P-type (mannose 6-phosphate receptor specific lectin), N-type (recognize mannose 6-phosphate N-glycans), R-type (contain structurally similar CRD to ricin), Collectins (collagen-containing C-type lectins), I-type (immunoglobulin type lectin), etc. Siglecs are a group of I-type lectins with sialic acid (Sia)-specificity and an amino-terminal. Such sialic acid specific lectins are of growing interest as reagents in biochemical research and diagnostic analysis and can be extremely useful to study sialic acids in diagnosis of pathogenic disease and tumors. The prevalence of such impressive sialic acid specific lectin with significant biomedical prospective is reported among arthropods and molluscs. Among these, the lectins of crabs were studied elaborately and almost all reported crab lectins, especially brachyuran crabs are of sialic acid specific. This chapter deliberates the lectins identified from anomuran and brachyuran crabs.
... Researchers are mainly focusing on marine natural products to produce new powerful and potential drugs including anti-HIV, anti-cancer, anti-microbials, and Alzheimer's therapeutics. Most of the bioactive compounds are organic compounds obtained from nature such as proteins, enzymes, large polymers, fatty acids, peptides, etc. Cyclic and linear peptides play a pivotal role in pharmaceutical development (Aneiros and Garateix 2004). Novel peptides from marine resources are become a new alternative for biomedical research due to their broad spectrum of activities. ...
Host–pathogen interactions are complex, governed by numerous factors such as host’s age, environment, behavior, immune system, and characteristics of the pathogen. The outcome of such a relationship depends on the resistance and susceptibility of the immune reactions of host. In fishes, there are two type immune responses, adaptive and innate. One of the key components of innate immune response is lectins. Lectins attach to the carbohydrate component of the glyco-proteins or lipids, proteoglycans, and are basically proteins. They not only mediate protein–carbohydrate interactions for the identification of infectious agents but also involved in biological activities of immune system like immobilization, agglutination, opsonization, and inactivation of pathogens. Studies on identification and characterization of lectins in fish are essential for prophylaxis, tracking, and treatment of diseases.KeywordsHost–pathogenImmune systemFish lectins
... [72] As the peptides in sponges are formed by the unusual condensation between amino acids, their structure is quite unique and are scarcely found in other terrestrial animals and microbes. [87] Red sea sponge Theonell swinhoei, contain a bicyclic glycopeptide, theonellamide G which exhibit strong antifungal activity against wild and amphotericin B-resistant strains of Candida albicans. [88] Several marine peptides are known to possess antitumor/cytotoxic properties. ...
There has been a growing demand towards alternative protein sources due to population growth and increasing consumer awareness on sustainability and environmental issues. Proteins from various plant, marine, insect and microbial sources are considered as excellent alternatives to substitute traditional animal-based proteins due their relatively low cost, sustainable production and nutritional value. This work is an overview of the physicochemical properties, functionality and nutritional quality of novel protein sources. Current information on the proximate composition, amino acid profile, digestibility, physicochemical
and functional properties is presented. Effects of extraction method
applied for obtaining protein ingredients from novel sources on protein
composition, functionality and nutritional quality are discussed. Findings of some of the recent studies focusing on modification of protein structure and improvement of functionality are reviewed. Potential end product applications and challenges related to the production and use of protein ingredients obtained from novel sources are discussed. Furthermore, future research recommendations are presented.
The numerous forms of extracellular polymeric substances (EPS) produced by soil algae, as well as their applications, are covered in different sections in this chapter. Algal biomass is mostly used to isolate EPS such as ulvans, carrageenan, alginates, proteins, and lipids. The commercial highlights of EPS are examined in detail in a separate section. In the last section of the chapter, frequent applications of EPS in bioremediation for wastewater treatment, i.e., removal of emerging toxins, at the laboratory scale, pilot scale, and industrial level are highlighted.
With the proceeding of global warming and water eutrophication, the phenomenon of green tide has garnered significant societal interest. Consequently, researchers had increasingly focused on the potential applications of green algae biomass, particularly its polysaccharides. The polysaccharide serves as the primary active constituent of green algae and has demonstrated numerous advantageous biological activities, including antioxidant, antiviral, anticoagulant, hypolipidemic and immuno-modulatory activities. The favorable bioavailability and solubility of green algae oligosaccharides are attributed to their low molecular weight. So there has been a growing interest in researching green algae polysaccharides and oligosaccharides for the utilization of marine biological resources. This review summarized the extraction, purification, chemical structure, composition, biological activity, and potential applications prospect of polysaccharides and oligosaccharides derived from green algae. The review could be helpful for expanding the applications of polysaccharides and oligosaccharides of green algae.
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The purpose of this study was to simultaneously analyze and validate phlorotannins, a group of functional compounds in Ecklonia cava, using HPLC–DAD. E. cava was profiled using UHPLC-Q-Orbitrap HRMS, and a total of six phlorotannin components were identified. Among these six compounds, phloroglucinol and dieckol were selected as marker components of E. cava, and a simultaneous analysis method using HPLC–DAD for phloroglucinol and dieckol was developed. Specificity, linearity, accuracy, precision, limit of detection (LOD), limit of quantification (LOQ), and matrix effect (ME) were verified using HPLC–DAD. These results complied with validation guidelines. The applicability of this simultaneous analysis method was confirmed by quantifying the contents of phloroglucinol and dieckol in E. cava samples (n = 10) purchased in Korea. This method can be used for quality control, such as standardization or determination of compounds in health functional foods containing E. cava extract.
The majority of bioactive polysaccharides are present in some marine creatures. These polysaccharides are considered as promising anti-obesity agents, their anti-obesity properties involve a number of mechanisms, including suppression of lipid metabolism and absorption, impact on satiety, and prevention of adipocyte differentiation. Obesity is linked to type 2 diabetes, cardiovascular disease, and other metabolic syndromes. In this review various bioactive polysaccharides like chitin, chitosan, fucosylated chondroitin sulphate, chitooligosaccharides and glycosaminoglycans have been discussed for their anti-obesity effects through various pathways. Critical evaluation of observational studies and intervention trials on obesity, lipid hypertrophy, dyslipidemia, and type 2 diabetes was done with a primary focus on specific marine fauna polysaccharide as a source of seafood that is consumed all over the world. It has been observed that consumption of individual seafood constituents was effective in reducing obesity. Thus, marine derived novel bioactive polysaccharides have potential applications in food and pharmaceutical industries.
Increased incomes, urbanization, and an aging population, are leading to changes in consumption patterns, resulting in a growing demand for proteins. From a sustainability perspective, there is a consensus that animal protein production has a disproportionately impact on the environment, particularly in intensive systems that require significant amounts of feed crops. Macroalgae have emerged as a promising feedstock for transitioning towards a blue bioeconomy. Red seaweed stands out as a particularly attractive action, as it can contain protein concentrations of up to 47 %, the highest among terrestrial plants and other algae divisions. These proteins offer a rich source of essential amino acids, making them excellent candidates for human food formulation. Nevertheless, compared to other major components such as carbohydrates, red macroalgae proteins remain underexploited. This review focuses on the potential of red algae as a protein source within an environmentally friendly biorefinery development strategy, primarily for food and biomedical applications. It also explores the strategies and limitations associated with protein extraction and purification, emphasizing the need for further in vivo and toxicological studies, particularly regarding the digestibility and bioavailability of red algal proteins
Algae, a complex group of photosynthetic organisms that range in size from single-celled microalgae to multicellular macroalgae, are crucial for the maintenance of a healthy ecosystem. They generate a large number of metabolites, which have a high value-added content and provide them a range of business opportunities. Algae provide a different renewable source for the synthesis of biopolymers and produce a variety of biopolymers due to their quick growth, high photosynthetic efficiency, and great potential for carbon dioxide fixation. As a reliable supply of protein, algae are frequently acknowledged, and their EAA composition satisfies FAO requirements. Microalgal peptides have also been associated with anti-ultraviolet (UV) radiation, anti-tumour, anti-atherosclerosis, hepatoprotective, and anti-tumour effects. Chlorophyll, carotenoids, and phycobiliproteins are just a few of the many pigments found in algae. These pigments, which range in colour from green to red, yellow, and brown, have been employed in food and cosmetics. In light of the foregoing, this article provides a synopsis of the industrial applications of pigments, proteins, and polymers in the food, cosmetics, and diagnostics sectors.KeywordsAlgaeAlgal polymersAlgal proteinsAlgal pigmentsIndustrial applications
Zonarol, which was discovered in the brown algae Dictyopteris undulata, has antibiotic, antioxidative, anti-inflammatory, and neuroprotective hydroquinone properties. Additionally, a daily treatment of zonarol taken orally has been proven to prevent ulcerative colitis and nonalcoholic fatty liver disease in experimentally induced mice models. In this study, to elucidate the physiological behavior of zonarol in vivo, the establishment of quantitative methods for the determination of zonarol in biological samples and basic pharmacokinetics parameters after oral or intravenous administration with purified zonarol to mice were investigated. The zonarol (20–600 ng/mL) in this study was dose-dependently detected using an HPLC-FI system as a single peak on the ODS column with 80% aqueous methanol at 332 nm with an excitation of 293 nm. The pharmacokinetic parameters were derived from a non-compartment analysis of the plasma concentration of zonarol following oral or intravenous treatment in mice. The absolute bioavailability of zonarol was calculated as 25.0%. Interestingly, the maximal distribution of zonarol in the brain (2.525 ± 1.334 µg/g tissue) at 30 min was observed to be higher and slower than that in the liver and kidney at 15 min after bolus intravenous administrations to the mice (10 mg/kg BW). Based on these results, zonarol might be a candidate for a potential drug, an effective tool for drug delivery, or enhancing the treatment of cerebral disease.
Bioprospecting of secondary metabolites is a key predictor for economic growth and development of a country. In the present study, we reviewed the trend of bioprospecting in Brazil focused on taxonomic groups. We use data published in the Web of Science and Scopus. Studies with this topic were published between 2004 and 2018, whose taxa, plants, microorganisms, insects, sponges, and amphibians were bioprospected, demonstrating significant growth in the number of publications (R² = 0.77; N = 67; p = 0.0006). As expected, plants dominated the citations scenario in the surveys, being the most well-known group (R² = 0.71; N = 40; p = 0.002), as a result of Brazil having the greatest species richness of plants in the world with great pharmacological use. The increase on the number of studies, especially in the kingdom Plantae, maximized the biotechnological applicability in the pharmaceutical industry. Microorganisms, including algae, bacteria and fungi also showed a significant increase in the number of publications (R² = 0.81; N = 34; p= 0.0002). Regarding the biotechnological applications of bioprospecting research in Brazil, the pharmaceutical industry accounted for the majority of the investigations (72.9 %), followed by agriculture (12.8 %), bioenergy industry (5.7 %), bioremediation (4.3 %), and food industry (4.3 %). The data indicate a promising scenario in the country's bioprospecting; however, insects, sponges and amphibians had a low number of published studies, making it impossible to perform a temporal analysis.
Coastal marine sediments are ecosystems rich in nutrients and microorganisms, these environments are considered to be highly competitive, so these microorganisms have developed strategies that allow them to regulate or inhibit the growth of other microbial populations. In sediments obtained from different locations in the La Paz Bay, in Baja California Sur México, different microorganisms have been identified that, according to their morphological, biochemical and molecular characteristics, belong to a group of Gram-positive bacteria known as actinobacteria. These bacteria have been shown to have the ability to grow in extreme conditions of low nutrient concentrations, and have the capacity of generating micro-ecosystems based on the production of secondary metabolites that allow them to develop properly in that ecosystem. Among the genera present in these ecosystems, the genus Streptomyces stands out. Cultures of this bacterium, extracellular extracts rich in peptides and other low molecular weight bioactive compounds have been obtained, which have been shown to have antimicrobial effect against different pathogenic strains. Thanks to the identification and characterization of the strains present in the microbial communities through massive sequencing techniques, it has been possible to infer the mechanisms by which these strains can carry out the synthesis of antimicrobial compounds. Knowing the genes involved in the synthesis of these metabolites, it is possible to design the appropriate mechanisms to carry out production at the laboratory level and to evaluate their activity using in silico and in vitro tools. The objective of this proposal is to describe the species of actinomycetes that have been identified in the bay, that present antimicrobial activity and that are potentially useful for their subsequent use at the semi-industrial level.
Mycobacterium leprae is the causative agent of Leprosy. Leprosy is the cause of Blindness in 3.2% of those affected by the disease. Blindness can have drastic consequence for those who probably already have sensory loss of the hand and feet. This disease is caused by Candida which is a normal flora that turns to a pathogenic one because of the Immunocompromised state. In a compromised individual serious sight threatening and life threatening infections may intervene. Present study aim to screen for ocular candidiasis among leprosy patients. The study group involves 40 male and 40 female. Ocular swabs were collected and
screened for the presence of Candidiasis using Hi-Chrome candida agar. Study documents prevalence of ocular candidiasis in age-wise and treatment-wise manner among leprosy patients. Study concludes the risk of ocular candidiasis among the leprosy patients due to immunocompramised condition of the host and improper co-ordination of optic nerves which provides sustainable platform for the establishment of ocular candidiasis. Proper and an effective therapeutic care need to emphasis/reduce the burden of blindness due to ocular candidiasis
In recent years, the healthcare community has faced challenges with viral infections, which they believe pose a significant threat to humanity. Because of the emergence and reemergence of these viral diseases, including the ongoing COVID-19 pandemic, there is an urgent need for novel drug discovery and potential antiviral therapeutics to combat these situations. Scientists are increasing focusing on marine-derived biomaterials, which have been shown to have a variety of effective antiviral activities, although there is some lag. This chapter highlights some of the studies that have been conducted on the antiviral activities of polysaccharides and antimicrobial peptides derived from marine organisms. It will specifically recall the antiviral activities of peptides and sulfated polysaccharides derived from the marine environment, such as tachyplesin, polyphemusin, chitin, chitosan, carrageenans, alginates, and fucans, among others. Furthermore, recent findings on the anti-SARS-CoV-2 action of some marine polysaccharides are also briefly summarized.
Seaweed has emerged as one of the most promising resources due to its remarkable adaptability, short development period, and resource sustainability. It is an effective breakthrough to alleviate future resource crises. Algal resources have reached a high stage of growth in the past years due to the increased output and demand for seaweed worldwide. Several aspects global seaweed farming production and processing over the last 20 years are reviewed, such as the latest situation and approaches of seaweed farming. Research progress and production trend of various seaweed application are discussed. Besides, the challenges faced by seaweed farming and processing are also analyzed, and the related countermeasures are proposed, which can provide advice for seaweed farming and processing. The primary products, extraction and application, or waste utilization of seaweed would bring greater benefits with the continuous development and improvement of applications in various fields.
Graphical Abstract
Most of the drugs used in medicine have been obtained from natural products or their synthetic derivatives. Bioactive peptides are an important group of natural product sources isolated from marine organisms, plants, animals, and microorganisms. Bioactive peptides have been investigated to promote health because of their high tissue affinity, specificity, and efficiency. Therefore, they possess a key role in cancer, including early diagnosis, prognostic predictors, and treatment. Anticancer effects of peptides have been widely investigated and shown to have many advantages as peptide-based drugs. Many naturally occurring peptides such as plitidepsin, dolastatin 10, didemnin B, and kahalalide F are used in clinical trials for the treatment of various cancers. The structure-activity relationship of these peptides can contribute to the design and development of peptide-based drugs. The aim of this chapter is to review the recent developments in bioactive peptides and their role in cancer therapy.
Seaweeds are considered one of the most potential yet renewable marine resources in the food, pharmacy, as well as cosmetic industries. A great deal of interest has been developed to extract bioproducts from seaweeds because of their numerous health-beneficial effects. Seaweed-derived bioproducts such as polysaccharides, fatty acids, natural pigments, proteins, and bioactive peptides exhibit many beneficial biological activities including antiviral, antioxidative, anticancer, brain development, neuroprotective, and immunomodulatory activities. However, in order to be used in pharmacological industries, green environmental-friendly technologies to refine bioproducts from seaweeds need to be developed. This contribution focuses on the development of bioproducts from seaweeds and elaborates the development of environmental-friendly technologies to extract bioproducts from seaweeds, their biological activities, health benefit effects, as well as potency in pharmacological industries.
This dissertation describes work undertaken towards a novel total synthesis of bistratamides J (1), E (2) and H (3), three related cyclic polypeptides isolated from the ascidian Lissoclinum bistratum.
All previous synthetic routes towards members of the bistratamide family have employed classic peptide chemistry, with macrocyclisation achieved via the formation of an amide bond. Here, a novel convergent route is investigated, using the formation of a thiazolidine as the key ring closing step, with subsequent oxidation furnishing the desired thiazole-containing products. This work describes the successful synthesis of the two component fragments and efforts towards their coupling.
Specific groups of sea anemone and scorpion toxins compete on the same pharmacological site, on the voltage-gated sodium channel of mammal excitable membranes. However, these scorpion and sea anemone toxins are two distinct protein families. Here we purified and sequenced a new sea anemone toxin, Bg II, highly toxic to mammals and also a less toxic mutant, Bg III. Two Bg II models were determined from sequence homologies with two sea anemone toxin two-dimensional NMR structures. Only one model conformed to circular dichroism data obtained from Bg II and was compared with an x-ray structure of a scorpion toxin. The comparison of the two structures shows that 5 amino acid residues are located similarly in the sea anemone toxin and the scorpion toxin. From these 5 residues, 4 are basic residues, constituting two distinct positively charged poles on the surface of these toxins. In the sea anemone mutant isolated, a negative charge beside one of the positive poles decreases the toxicity. These results show that positively charged amino acid residues could be essential for the activity of these toxins and outline the role of electrostatic bonds in the interaction of sea anemone and scorpion toxins with their receptor.
Six new guanidine compounds, named minalemines A-F2, were isolated from the marine tunicate Didemnun rodriguesi by careful HPLC separation. Their structures were elucidated by MS, 1D- and 2D-NMR spectral analysis, and chemical degradation. These compounds incorporate one agmatine (Agma) and one homoagmatine (Hagma) terminal unit with their guanidine groups free and the primary amino groups linked through a peptidic bond to L-Leu and a very rare β-N-carboxymethyl amino acid (Ncma) bearing a saturated long chain. The saturated chains of minalemines A-C are homologs (C7, C8, and C9 respectively). Minalemines D-F are the sulfamic acid derivatives of minalemines A-C and constitute the first examples of such a functional group in a marine organism.
Cone snails are tropical marine mollusks that envenomate prey with a complex mixture of neuropharmacologically active compounds.
We report the discovery and biochemical characterization of a structurally unique peptide isolated from the venom of Conus marmoreus. The new peptide, mr10a, potently increased withdrawal latency in a hot plate assay (a test of analgesia) at intrathecal
doses that do not produce motor impairment as measured by rotarod test. The sequence of mr10a is NGVCCGYKLCHOC, where O is 4-trans-hydroxyproline. This sequence is highly divergent from all other known conotoxins. Analysis of a cDNA clone encoding the
toxin, however, indicates that it is a member of the recently described T-superfamily. Total chemical synthesis of the three
possible disulfide arrangements of mr10a was achieved, and elution studies indicate that the native form has a disulfide connectivity
of Cys1-Cys4 and Cys2-Cys3. This disulfide linkage is unprecedented among conotoxins and defines a new family of Conus peptides.
The world of nature provides a never-ending set of fascinating problems for the chemist. Many of the most intriguing problems, however, concern compounds available in only truly minute quantities. One solution is to focus on bioassay-guided separations. In so doing one can isolate compounds with novel structures or unsuspected activities from almost any phylum, including tunicates, sponges, insects, or even the much-studied terrestrial plants, as exemplified in several recent studies in our laboratory involving activities ranging from antiviral and antimicrobial activity to cytotoxicity and immunomodulation. Moreover, newer spectroscopic techniques, especially fast atom bombardment mass spectrometry and tandem mass spectrometry, enhance one's ability to study compounds present in minute quantities, including those of importance to the host organism, such as neuropeptides in insects or marine invertebrates.
Phycobiliproteins are brilliantly colored, highly fluorescent components of the photosynthetic light-harvesting antenna complexes of cyanobacteria (blue-green algae), red algae and cryptomonads. These proteins carry covalently attached linear tetrapyrrole pigments related structurally to biliverdin. Phycobiliproteins, purified from certain organisms, are isolated as either trimers, ()3, of approximatelyM
r 110–120103 (e.g., allophycocyanins), or hexamers, ()6, of aboutM
r 250103 (certain phycoerythrins). Three phycobiliproteins R-phycoerythrin, B-phycoerythrin, and allophycocyanin serve as valuable fluorescent tags with numerous applications in flow cytometry, fluorescence activated cell sorting, histochemistry and, to a limited degree, in immunoassay and detection of reactive oxygen species. These applications exploit the unique physical and spectroscopic properties of phycobiliproteins.
We studied the effects of BgK toxin on outward K+ currents in isolated neurons of the snail Helix aspersa, using the whole cell patch clamp technique. BgK partially and reversibly blocked K+ currents in the 1 pM to 100 nM concentration range (n=53). The dose–response curve for BgK current inhibition had a maximum blocking effect at 100 nM. Our results indicate that BgK is a potent, apparently non-selective, K+ channel blocker in molluscan neurons.
Sea anemone venom is known to contain toxins that are active on voltage-sensitive Na+ channels, as well as on delayed rectifier K+ channels belonging to the Kv1 family. This report describes the properties of a new set of peptides from Anemonia sulcata that act as blockers of a specific member of the Kv3 potassium channel family. These toxins, blood depressing substance (BDS)-I and BDS-II, are 43 amino acids long and differ at only two positions. They share no sequence homologies with other K+ channel toxins from sea anemones, such as AsKS, AsKC, ShK, or BgK. In COS-transfected cells, the Kv3.4 current was inhibited in a reversible manner by BDS-I, with an IC50 value of 47 nM. This inhibition is specific because BDS-I failed to block other K+ channels in the Kv1, Kv2, Kv3, and Kv4 subfamilies. Inward rectifier K+ channels are also insensitive to BDS-I. BDS-I and BDS-II share the same binding site on brain synaptic membranes, with K0.5 values of 12 and 19 nM, respectively. We observed that BDS-I and BDS-II have some sequence homologies with other sea anemone Na+ channels toxins, such as AsI, AsII, and AxI. However, they had a weak effect on tetrodotoxin-sensitive Na+ channels in neuroblastoma cells and no effect on Na+ channels in cardiac and skeletal muscle cells. BDS-I and BDS-II are the first specific blockers identified so far for the rapidly inactivating Kv3.4 channel.
Onchidin B (4) is a cyclic depsipeptide isolated from the pulmonate mollusc Onchidium sp. Its structure was determined by extensive 2D-NMR, FABMS, tandem FAB MS/MS, selective hydrolysis, and synthesis. It contains four alpha-amino acids [two units of N-methyl valine (MeVal), two units of proline (Pro)], four alpha-hydroxy acids [two 2-hydroxyisovaleric acids (Hiv), two 2-hydroxy-3-methylpentanoic acid moieties (Hmp)] and two units of the new beta-hydroxy acid: 3-hydroxy-2-methyloct-7-ynoic acid (Hymo)]. Selective hydrolysis and direct comparison by chiral CC-MS with authentic samples of the alpha-amino and alpha-hydroxy acids allowed us the assignment of the entire absolute stereochemistry of onchidin B. In this way, the alpha-hydroxy acids were found to be (S)-Hiv and (S,S)-Hmp, and the a-amino acids (R)-proline, (S)-proline, and (R)-MeVal. In order to establish the absolute configuration of the new beta-hydroxy acid, Hymo, its four possible stereoisomers were stereoselectively synthesized using chiral N-propionyl oxazolidinones and hex-5-ynal as starting material. Comparison by HPLC-MS of the synthetic samples with the natural Hymo (all derivatized as esters of (-)-(R)-alpha-methoxy-alpha-(9-anthryl) acetic acid), affirmed its absolute stereochemistry as (2R,3R). Thus, onchidin B (4) is cycle [(R)-MeVal-(R,R) -Hymo-(S)-Pro-(S,S)-Hmp-(S)-Hiv-(R)-MeVal-(R,R)-Hymo-(R)-Pro-(S,S)-Hmp-(S)-H . It is formed by a head-to-tail linkage of two halves, each one built by five units and identical sequence. The lack of symmetry of onchidin B is thus due to the presence of one (S)-Pro unit in one half and one (R)-Pro unit in the other. The structural similarity between onchidin B (4) and onchidin (2), both isolated from the same organism, and between the beta-hydroxy acid Hymo (5) and the beta-amino acid Amo (3) found in onchidin is noticed.
A procedure is described for the preparation of stable phycobilisomes from the unicellular cyanobacterium Synechococcus sp. 6301 (also known as Anacystis nidulans). Excitation of the phycocyanin in these particles at 580 nm leads to maximum fluorescence emission, from allophycocyanin and allophycocyanin B, at 673 nm. Electron microscopy shows that the phycobilisomes are clusters of rods. The rods are made up of stacks of discs which exhibit the dimensions of short stacks made up primarily of phycocyanin (Eiserling, F. A., and Glazer, A. N. (1974) J. Ultrastruct. Res. 47, 16-25). Loss of the clusters, by dissociation into rods under suitable conditions, is associated with loss of energy transfer as shown by a shift in fluorescence emission maximum to 652 nm. Synechococcus sp. 6301 phycobilisomes were shown to contain five nonpigmented polypeptides in addition to the colored subunits (which carry the covalently bound tetrapyrrole prosthetic groups) of the phycobiliproteins. Evidence is presented to demonstrate that these colorless polypeptides are genuine components of the phycobilisome. The nonpigmented polypeptides represent approximately 12% of the protein of the phycobilisomes; phycocyanin, approximately 75%, and allophycocyanin, approximately 12%. Spectroscopic studies that phycocyanin is in the hexamer form, (alpha beta)6, in intact phycobilisomes, and that the circular dichroism and absorbance of this aggregate are little affected by incorporation into the phycobilisome structure.
Conus venoms contain a remarkable diversity of pharmacologically active small peptides. Their targets are ion channels and receptors in the neuromuscular system. The venom of Conus geographus contains high-affinity peptides that act on voltage-sensitive calcium channels, sodium channels, N-methyl-D-aspartate (NMDA) receptors, acetylcholine receptors, and vasopressin receptors; many more peptides with still uncharacterized receptor targets are present in this venom. It now seems that the Conus species (approximately 500 in number) will each use a distinctive assortment of peptides and that the pharmacological diversity in Conus venoms may be ultimately comparable to that of plant alkaloids or secondary metabolites of microorganisms. The cone snails may generate this diverse spectrum of venom peptides by a "fold-lock-cut" synthetic pathway. These peptides are specific enough to discriminate effectively between closely related receptor subtypes and can be used for structure-function correlations.
Dolastatin 10, a potent antimitotic peptide from a marine animal, strongly inhibits microtubule assembly, tubulin-dependent GTP hydrolysis, and the binding of vinca alkaloids to tubulin. In studies of the binding of [3H]vincristine to the protein, with vinblastine as a control for competitive inhibition (Ki, 6.6 microM), we found that the macrolide antimitotic agents maytansine and rhizoxin were also competitive inhibitors (Ki values, 3.1 and 12 microM). Dolastatin 10 and an unrelated peptide antimitotic, phomopsin A, were more potent but noncompetitive inhibitors (Ki values, 1.4 and 2.8 microM). Since maytansine and, to a much lesser extent, vinblastine interfere with nucleotide exchange on tubulin, all drugs were examined for effects on nucleotide interactions at the exchangeable GTP site. Rhizoxin had effects intermediate between those of vinblastine and maytansine. Both peptides inhibited binding of radiolabeled GTP to tubulin even more strongly than did maytansine, but no drug displaced nucleotide from tubulin. The drugs were evaluated for stabilizing effects on the colchicine binding activity of tubulin. The peptides prevented loss of this activity, and vinblastine provided partial protection, while rhizoxin and maytansine did not stabilize tubulin. A tripeptide segment of dolastatin 10 also effectively inhibits tubulin polymerization and GTP hydrolysis. The tripeptide did not significantly inhibit either vincristine binding or nucleotide exchange, nor did it stabilize colchicine binding. These findings are rationalized in terms of a model with two distinct drug binding sites in close physical proximity to each other and to the exchangeable GTP site on beta-tubulin.
In the search for antitumor metabolites from marine sponges, a number of novel peptides with unique structures and activities have been identified. Peptides belonging to several structural series have been found and these peptides often contain unusual amino acids, which are either rare in terrestrial and microbial systems or which are novel to science. The development of new NMR techniques and chemical methods for stereochemistry determination has assisted in the structure determination of these complex compounds. The similarity of some of these peptides to microbial metabolites illustrates the need for further research into the symbiotic microbial association within these organisms.
The venom of predatory marine snails is a rich source of natural products that act on specific receptors and ion channels
within the mammalian nervous system. A 41–amino acid peptide, σ-conotoxin GVIIIA, was purified on the basis of its ability
to inactivate the 5-HT3 receptor, an excitatory serotonin-gated ion channel. σ-Conotoxin contains a brominated tryptophan residue, which may be important
for peptide activity because the endogenous ligand for the 5-HT3 receptor is a hydroxylated derivative of tryptophan. σ-Conotoxin inactivates the 5-HT3 receptor through competitive antagonism and is a highly selective inhibitor of this receptor. Serotonin receptors can now
be included among the molecular targets of natural polypeptide neurotoxins.
Arenastatin A (1) has been isolated from the Okinawan marine sponge Dysidea arenaria and the chemical structure including parts of the absolute configurations elucidated. Arenastatin A (1) is a cyclic didepsipeptide and exhibited extremely potent cytotoxicity against KB cells at IC50 5 pg/ml.
The tissues of the common North Atlantic sea anemone, Metridium senile, contain an agent capable of lysing mammalian cells. The active substance, metridiolysin, was purified and found to be a protein of molecular weight approx. 80 000 and to be isoelectric at approx. pH 5.0. It is thermolabile and is inactivated by Pronase and subtilisin. The optimal pH for hemolysis is between 5 and 6, and at pH 8.0 or higher the lysin is inactive. It can be dissociated into two subunits of unequal size. Metridiolysin destroys blood platelets in vitro as well as cultured fibroblasts, and is lethal when injected intravenously into mice. It is not lytic for bacterial protoplasts and spheroplasts. Hemolysis is specifically prevented by cholesterol. Erythrocytes from the horse and dog are approx. 100 times as sensitive to lysis as those from the mouse, and erythrocytes from other animals tested are intermediate in sensitivity.
UpI is a basic protein purified from the crude extract of the sea anemone Urticina piscivora. As a potent positive inotrope, it increases the force of contraction of the left atria of the heart of rat and guinea-pig with little or no increase in heart rate in vitro. It also elicited ileal contractions similar to acetylcholine and such action was inhibited by atropine. Intravenous administration (direct invasive blood pressure studies) of UpI (0.1–20 μg/kg body weight) produced a fall in blood pressure (BP) in normotensive rats. This fall in BP was further reduced by atropine (1 mg/kg) but not completely abolished. Postmortem findings of the internal organs revealed severe haemorrhage, oedema and necrosis to the lung and skin but to a lesser extent on the kidney and liver. No histological alteration was observed in the brain or heart. © 1997 John Wiley & Sons, Ltd.
Halicylindramides A-C (1-3) have been isolated from the Japanese marine sponge Halichondria cylindrata. They are tetradecapeptides with the N-terminus blocked by a formyl group and the C-terminus lactonized with a threonine residue. Their total structures including absolute stereochemistry were determined by a combination of spectral and chemical methods. Halicylindramides A-C were antifungal against Mortierella ramanniana and cytotoxic against P388 murine leukemia cells.
Chemical investigation of the marine red alga (Rhodophyta) Ceratodictyon spongiosum containing the symbiotic sponge Sigmadocia symbiotica collected from Biaro Island, Indonesia, yielded two isomers of a new and bioactive thiazole-containing cyclic heptapeptide, cis, cis-ceratospongamide (1) and trans,trans-ceratospongamide (2). Isolation of these peptides was assisted by bioassay-guided fractionation using a brine shrimp toxicity assay (Artemia salina). The structures of the ceratospongamides, which each consist of two L-phenylalanine residues, one (L-isoleucine)-L-methyloxazoline residue, one L-proline residue, and one (L-proline)thiazole residue, were established through extensive NMR spectroscopy, including H-1-C-13 HMQC-TOCSY, and H-1-N-15 HMBC experiments, as well as chemical degradation and chiral analysis. cis,cis- and trans,trans-ceratospongamide are stable conformational isomers of the two proline amide bonds. Molecular modeling of these two ceratospongamide isomers showed the trans, trans isomer to be quite planar, whereas the cis, cis isomer has a more puckered overall conformation. trans, trans-Ceratospongamide exhibits potent inhibition of sPLA(2) expression in a cell-based model for antiinflammation (ED50 32 nM), whereas the cis,cis isomer is inactive. trans, trans-Ceratospongamide was also shown to inhibit the expression of a human-sPLA(2) promoter-based reporter by 90%.
Three new cyclic peptides, microsclerodermins C - E (3–5), were isolated from two species of lithistid sponges from the Visayan Islands, Philippines. The sponge Theonella sp. contained peptides 3 and 4, while Microscleroderma sp. contained peptides 4 and 5. Their structures, which feature three unprecedented amino acids, were elucidated using spectroscopic methods and chemical degradation.
The novel cyclic depsipeptides papuamides A (1), B (2), C (3), and D (4) have been isolated from Papua New Guinea collections of the sponges Theonella mirabilis and Theonella swinhoei. Their structures were determined by a combination of spectroscopic analysis and chemical degradation and derivatization studies. In addition to glycine, alanine, and threonine, these peptides contain a number of unusual amino acids including 3,4-dimethylglutamine, β-methoxytyrosine, 3-methoxyalanine, and 2,3-diaminobutanoic acid or 2-amino-2-butenoic acid residues. Papuamides A−D (1−4) are also the first marine-derived peptides reported to contain 3-hydroxyleucine and homoproline residues. These peptides also contain a previously undescribed 2,3-dihydroxy-2,6,8-trimethyldeca-(4Z,6E)-dienoic acid moiety N-linked to a terminal glycine residue. Papuamides A (1) and B (2) inhibited the infection of human T-lymphoblastoid cells by HIV-1RF in vitro with an EC50 of approximately 4 ng/mL. Compound 1 was also cytotoxic against a panel of human cancer cell lines with a mean IC50 of 75 ng/mL.
Red tides resulting from blooms of the dinoflagellate Ptychodiscus brevis in the Gulf of Mexico have elicited a great deal of scientific interest since the first documented event over 100 years ago (1). Human intoxications from the ingestion of contaminated shellfish and the impact of massive fish kills on the tourist industry along the Gulf coast of the United States have resulted in a concerted research effort to understand the genesis of red tides and to isolate and characterize the toxins of P. brevis. Methods of detection, metabolism, and pathophysiology of the brevetoxins, PbTx-2 and PbTx-3, are summarized. Infrared spectroscopy and innovative chromatographic techniques were examined as methods for detection and structural analysis. Toxicokinetic and metabolic studies for in vivo and in vitro systems demonstrated hepatic metabolism and biliary excretion. An in vivo model of brevetoxin intoxication was developed in conscious tethered rats. Intravenous administration of toxin resulted in a precipitous decrease in body temperature and respiratory rate, as well as signs suggesting central nervous system involvement. A polyclonal antiserum against the brevetoxin polyether backbone was prepared; a radioimmunoassay was developed with a sub-nanogram detection limit. This antiserum, when administered prophylactically, protected rats against the toxic effects of brevetoxin.
A new cell growth inhibitory (P-388 murine leukemia ED50 7.5 micrograms/ml) cycloheptapeptide designated phakellistatin 1 was isolated from two Indo-Pacific sponges, Phakellia costata and Stylotella aurantium. Structural elucidation was accomplished utilizing high field nmr, amino acid analyses, and mass spectral techniques (fab, tandem ms/ms), followed by chiral gas chromatographic procedures for absolute configuration assignments (all S-amino acid units). By these methods phakellistatin 1 [1] was found to be cyclo (Pro-Ile-Pro-Ile-Phe-Pro-Tyr), and this assignment was finally confirmed by an X-ray crystal structure determination.
A sponge of the lithistid family Theonellidae from southern Mozambique contained the known compound aurantoside A (1) together with two new cyclic peptides, mozamides A (2) and B (3). The structures and absolute configurations of mozamides A and B, which contain a rare ureido group, were determined by interpretation of spectral data and chiral GC−MS analysis of the amino acids resulting from acid-catalyzed hydrolysis.
Theopalauamide (1) is the major bicyclic peptide from the symbiotic filamentous eubacteria that are found in the interior of Theonella swinhoei from Palau. It was also isolated from T. swinhoei from Mozambique. The structure of theopalauamide was determined by analysis of spectroscopic data, and its stereochemistry was determined by chemical degradation and analysis of the products by chiral GC-MS. The minor peptide, isotheopalauamide (2), was shown to be a stable conformational isomer that was formed by TFA-catalyzed equilibration during the isolation procedure.
Theonegramide (2) is an antifungal glycopeptide consisting of arabinose joined to a bicyclic dodecapeptide that contains the unusual amino acids β-hydroxyasparagine, isoserine, α-aminoadipic acid, 4′-bromo-3-methylphenylalanine, 3-amino-4-hydroxy-6-methyl-8-phenylocta-5,7-dienoic acid, and the same histidinoalanine moiety previously observed in theonellamide F (1). The structure of theonegramide (2) was elucidated by analysis of spectral data and its absolute configuration was determined by GC-MS analysis using a chiral column packing.
The lithistid sponge Aciculites orientalis contains three cyclic peptides, aciculitins A−C (1−3), that are identical except for homologous lipid residues. The structure of the major peptide, aciculitin B (2), was elucidated by interpretation of spectroscopic data. The aciculitins consist of a bicyclic peptide that contains an unusual histidino-tyrosine bridge. Attached to the bicyclic peptide are C13−C15 2,3-dihydroxy-4,6-dienoic acids bearing d-lyxose at the 3-position. The structures of aciculitamides A (4) and B (5), which are artifacts obtained earlier from this sponge, are also presented. The aciculitins 1−3 inhibited the growth of Candida albicans and were cytotoxic toward the HCT-116 cell line.
A novel antifungal peptide, theonellamide F, was isolated from a marine sponge, genus Theonella. It is a dodecapeptide composed of L-Asn, L-aThr, two residues of L-Ser, L-Phe, βAla, (2S,3R)-3-hydroxyasparagine, (2S,4R)-2-amino-4-hydroxyadipic acid, τ-L-histidino-D-alanine, L-p-bromophenylalanine, and (3S,4S,5E,7E)-3-amino-4-hydroxy-6-methyl-8-(p-bromophenyl)-5,7-octadienoic acid. Its bicyclic structure including absolute stereochemistry was unequivocally determined as 1, which contains an unprecedented histidinoalanine bridge.
A highly methylated cytotoxic tripeptide, milnamide A (I), along with jasplakinolide was isolated from Papua New Guinean collections of the Axinellida sponge A. cf. constricta
This chapter presents information on some of the most common natural toxins, their mechanisms of action, and some modern principles of their treatment. It discusses: differences between poisons, toxins, and venoms; major sites and mechanisms of toxin action; important microbial, plant, and animal toxins; animal venoms and their active constituents; plants and animals causing contact dermatitis; and strategies for treating intoxications.
Equinatoxin II is a cytolytic polypeptide from the sea anemone Actinia equina L. which forms pores in natural and artificial membranes. The intrinsic fluorescence of its five tryptophanyl residues was used to monitor the conformational changes induced by denaturing agents, pH and lipids. In the presence of denaturants, the emitted fluorescence peak, normally occurring at 335 nm, was reduced in height by about 65% and red-shifted to 354 nm indicating unfolding. The toxin fluorescence intensity reversibly decreased by increasing the pH, whereas lipid vesicles, at every pH, caused an increase and a blue shift. The amount of toxin binding to the lipid vesicle was increased by the presence of sphingomyelin. With sphingomyelin-containing vesicles half-saturation occurred at a lipid/toxin molar ratio of about 40, whereas with phosphatidylcholine no saturation appeared up to a ratio of 300. One hydrophilic neutral quencher (acrylamide) and two lipid-confined phosphatidyltype quenchers [bis(9,10-dibromostearoyl)-sn -glycero-3-phosphocholine and 1-palmitoyl-2-(l-pyrenedecanoyl)-sn -glycero-3-phosphocholinel were used to assess the exposure of the emitting centres to the solvent and/or to the lipid. Most of the indolyl residues were found to be solvent-exposed in the water-soluble form of the toxin, as inferred from acrylamide quenching. Upon association with lipid vesicles, the fraction accessible to acrylamide dropped considerably, meanwhile the toxin became sensitive to lipid-soluble quenchers. Taken together these results suggest that insertion of equinatoxin II into sphingomyelin-containing bilayers is facilitated by high pH and results in the transfer of one or more exposed tryptophanyl residues into the lipid phase. Calcein-loaded vesicles, with or without a lipid quencher, were used to monitor simultaneously the formation of pores and the transfer of the tryptophans to the lipid phase. We found that the rate constants for vesicles permeabilization and for changes of intrinsic tryptophanyl fluorescence had a different dependence on the lipid/toxin ratio suggesting they correspond to separate steps in the toxin lipid interaction.
A new class of K channel peptide toxin has been found in sea anemones. So far, four homologous short toxins possessing 35–37 residues and 3 disulfide bonds have been isolated and sequenced. The two most thoroughly investigated members of this toxin group are ShK and BgK. The covalent structures of these toxins display no homology with the scorpion K toxins and their disulfide bonding pattern is also different. The NMR-derived solution structures of ShK and BgK toxins are similar in that two short alpha-helices are present, in contrast to the predominantly beta-sheet structures found in scorpion toxins. While BgK blocks Kv1.1,1.2 and 1.3 homomeric channels almost equipotently at 6–15 nM concentrations, ShK blocks Kv1.1 and 1.3 channels at very low (20–100 pM) concentrations and Kv1.2 at a much higher (>10 nM) concentration. The sea anemone peptides also interact with Kv1 heteromers present in rat brain membranes. Additionally, ShK has been shown to block intermediate conductance K(Ca) channels in lymphocytes and erythrocytes. Kv1.3 homomers are localized largely on the surfaces of T-lymphocytes; scorpion toxin blockade of these channels has been shown to inhibit proliferation of these cells in vitro and the development of delayed type hypersensitivity reaction and antibody formation in response to an allogeneic challenge in vivo. ShK toxin also inhibits in vitro lymphocyte proliferation in response to an antibody directed to a lymphocyte membrane antigen. The homomeric lymphocyte Kv1.3 and heteromeric brain Kv1 channel binding domains of ShK and BgK have been located by alanine scans of analogs prepared by solid-phase peptide synthesis. Both toxins possess a receptor-binding hot spot consisting of a sequentially contiguous Lys-Tyr diad on the second helical segment which spatially resembles a diad consisting of Lys27 and Tyr36 attached to a beta-sheet scaffold in charybdotoxin and related scorpion toxins. From analysis of the structural requirements for blocking Kv1.3 homomers and brain Kv1 heteromers, ShK analogs possessing even greater selectivity for the Kv1.3 channel have been designed. These peptides and smaller peptide-mimetic compounds incorporating the anemone toxin pharmacophore are being developed as potential immunosuppressant agents.
α-Conotoxins (α-CgTxs) are a family of Cys-enriched peptides found in several marine snails from the genus Conus. These small peptides behave pharmacologically as competitive antagonists of the nicotinic acetylcholine receptor (AChR). The data indicate that (1) α-CgTxs are able to discriminate between muscle- and neuronal-type AChRs and even among distinct AChR subtypes; (2) the binding sites for α-CgTxs are located, like other cholinergic ligands, at the interface of α and non-α subunits (γ, δ, and ε for the muscle-type AChR, and β for several neuronal-type AChRs); (3) some α-CgTxs differentiate the high- from the low-affinity binding site found on either α/non-α subunit interface; and that (4) specific residues in the cholinergic binding site are energetically coupled with their corresponding pairs in the toxin stabilizing the α-CgTx-AChR complex. The α-CgTxs have proven to be excellent probes for studying the structure and function of the AChR family.
-Three agglutinins have been isolated from the aqueous ethanolic extract of the marine red alga Solieria robusta by precipitation with cold ethanol, gel filtration and ion-exchange HPLC. These new proteins, designated solnins A, B and C, were monomeric glycoproteins with a similar Mr of 23 000 from gel filtration and 29 000 from SDS-electrophoresis, and they shared such predominant amino acids as Gly, Asx and Glx. However, solnins A, B and C had different isoelectric points of 4.3, 4.2 and 4.1, respectively. From electrophoretic analyses of these agglutinins on polyacrylamide gels of various concentration, they were confirmed to be isoagglutinins. The ratio of the yields of solnins A, B and C was ca 1:3:1. Solnins strongly agglutinated rabbit erythrocytes, but did not agglutinate human erythrocytes and mouse FM3A tumour cells. Treatment of the rabbit erythrocytes with trypsin or pronase effected their sensitivity to hemagglutination by the agglutinins. The hemagglutinating activity of the solnins was inhibited by glycoproteins bearing N- glycosidic sugar chains, but not by any mono- and oligosaccharides tested. The activity was not affected by divalent cations. Solnins also showed mitogenic activity for mouse splenic lymphocytes, while they inhibited the growth in vitro of mouse leukaemia cells L1210 or mouse FM3A tumour cells.
Isolation and structure elucidation of three peptide antibiotics, discodermins B, C, and D, from the marine sponge, Discodermia kiiensis, and the revised structure of discodermin A are described.
R. S. Norton. Review article—Structure and structure-function relationships of sea anemone proteins that interact with the sodium channel. Toxicon29, 1051–1084, 1991.—Sea anemones produce a series of toxic polypeptides and proteins with molecular weights in the range 3000–5000 that act by binding to specific receptor sites on the voltage-gated sodium channel of excitable tissue. This article reviews our current knowledge of the molecular basis for activity of these molecules, with particular emphasis on recent results on their receptor binding properties, the role of individual residues in activity and receptor binding, and their three-dimensional structures as determined by nuclear magnetic resonance spectroscopy. A region of these molecules that constitutes at least part of the receptor binding domain is proposed.
Marine cone snails have developed many distinct venoms that contain biologically active peptides as part of an envenomation survival strategy for feeding and defense. These peptides, known as conopeptides, have been optimized through evolution to target specific ion channels and receptors with very high affinities and selectivities. Side effects of currently available therapies often arise from their lack of selectivity between pharmacologically relevant targets and targets that have a similar structure but different function. As conopeptides can be highly selective between closely related receptor subtypes, they could meet specific therapeutic needs with a reduced likelihood of side effects.
kappa-Conotoxin PVIIA from the venom of Conus purpurascens is the first cone snail toxin that was described to block potassium channels. We synthesized chemically this toxin and showed that its disulfide bridge pattern is similar to those of omega- and delta-conotoxins. kappa-conotoxin competes with radioactive alpha-dendrotoxin for binding to rat brain synaptosomes, confirming its capacity to bind to potassium channels; however, it behaves as a weak competitor. The three-dimensional structure of kappa-conotoxin PVIIA, as elucidated by NMR spectroscopy and molecular modeling, comprises two large parallel loops stabilized by a triple-stranded antiparallel beta-sheet and three disulfide bridges. The overall fold of kappa-conotoxin is similar to that of calcium channel-blocking omega-conotoxins but differs from those of potassium channel-blocking toxins from sea anemones, scorpions, and snakes. Local topographies of kappa-conotoxin PVIIA that might account for its capacity to recognize Kv1-type potassium channels are discussed.
Three toxic polypeptides, Toxins I, II and III have been isolated from the sea anemone Anemonia sulcata Pennant (Actinaria). Toxin isolation was accomplished by alcoholic extraction of the homogenized sea anemones, batchwise adsorption on cation exchangers, gel filtration on Sephadex (G 50, G 25, G 10) and ion exchange chromatography on SP-Sephadex and QAE-Sephadex. It was demonstrated that the same toxins (Toxin I and Toxin II) are also present in the separated tentacles. Toxin I contains 45 amino acids, mol. wt 4702, Toxin II contains 44 amino acids, mol. wt 4197, Toxin III contains 24 amino acids, mol. wt 2678.The toxins were tested on the shore crab Carcinus maenas by intramuscular injection. For both Toxins I and II the lethal dose is less than 2 μg per kg Carcinus, whereas for Toxin III it is less than 50 μg per kg. Toxins I and II also have a strong paralysing effect on mammals and fishes.
Five species of toxic pelagic marine coelenterates (Physalia physalis, the Portuguese man-o' war; Chrysaora quinquecirrha, the sea nettle; Chironex fleckeri, the sea wasp; Chiropsalmus quadrigatus, also called the sea wasp and Stomolophus meleagris, the cabbage head jellyfish) have recently been studied. Two of these animals can be lethal to man and two others produce painful cutaneous stings, of varying severity. All five species possess a significant cardiotoxic activity to mice and are lethal to lower animals. This action may be induced by an abnormality in ionic transport across membranes. Calcium ion and perhaps sodium ion transport appear to be important targets of these toxins. The pain in humans produced by the venoms of these animals may be induced by a large molecular weight polypeptide which has a kinin-like action. Although many of the venoms possess other mediators of inflammation, such as histamine, serotonin, prostaglandins or compounds which result in their release, no consistency between the severity of the sting and the abundance of these substances is apparent.
Marine macroorganisms and microorganisms, like terrestrial species, produce a dizzying array of secondary metabolites, including terpenes, steroids, polyketides, peptides, alkaloids and porphyrins. Most of the marine metabolites are found in terrestrial species as such or have close counterparts in land-based species, but some are sufficiently unusual to constitute a separate class (e.g. marine sterols). Although in many cases the functions of these secondary metabolites in the marine species themselves are unclear, other compounds play well-defined roles-for example as trail markers, sexual attractants, antifouling substances or antifeedants. What is clear is that many of the most interesting marine secondary metabolites have potent activities largely unrelated to their in situ roles. Examples abound of antitumour, antiviral, immunosuppressive and antimicrobial agents, as well as neurotoxins, hepatotoxins and cardiac stimulants. Relatively few biosynthetic studies of marine secondary metabolites have been done because of the logistical problems of working under water and the primitive state of techniques for growing marine invertebrates in culture. However, recent studies indicate that many compounds isolated from marine macrospecies (e.g. sponges) may instead be produced by microorganisms (e.g. bacteria or phytoplankton). Studies of these symbionts may facilitate efforts to understand the biosyntheses of these metabolites.
1. The effects of a high molecular weight toxin isolated from the sea anemone Condylactis gigantea (Condytoxina 2) on the cholinergic responses were studied in two different preparations: identified cells of a land snail and enzymatically dissociated mice sensory neurons. These neurons were studied using intracellular recording and concentration clamp techniques respectively. 2. The toxin produces a concentration-dependent dual effect on the cholinergic responses in both preparations. Thus the application of the toxin at concentrations up to 25 nmol/l produces a reversible block of the response whereas higher doses potentiates it. 3. These results suggest that Condytoxina 2 contains an active compound(s) with the capacity to bind to the nicotinic acetylcholine receptor of excitable cells in both snail and mice neurons. During this action complex allosteric interactions among the binding sites could occur.
The sponge Axinella polypoides contains four different D-galactose binding lectins and one, termed lectin IV, which is specific for hexuronic acids. Only the D-galactose binding lectins were investigated in this study. The complete amino-acid sequence of lectin I, the main component in the crude extract was determined. Lectin I is a homodimer and each subunit comprises 144 amino acids with a M(r) of 15,847 +/- 10, as calculated from the sequence data and determined by mass spectrometry. Each subunit contains one intrachain disulfide bridge between positions 4 and 46. Of lectin II, only the first 49 amino acids of the NH2-terminal end were analysed. This part has 29 amino acids in common with lectin I, including a cysteine residue at position 4, also suggesting an intrachain loop in a identical position as in lectin I. The molecular mass of its subunit is 16,235 +/- 10 Da. Only the first 15 NH2-terminal amino acids of lectins III and V could be sequenced. Lectin V was identical to lectin II in all positions, whereas lectin III showed only 5 residues identical to lectins I or II. Thus, lectins I, II and III are derived from three different genes, whereas lectin V may either be a proteolytic cleavage product, or result from different splicing events or may be derived also from a separate gene. Neither of the four lectins showed any similarity to known lectin sequences of animal or plant origin.