Fernando Albericio

University of KwaZulu-Natal | ukzn · Department of Chemistry and Physics

A total of 37 new drug entities were approved in 2022. Although this year registered the lowest number of drug approvals since 2016, the TIDES class consolidated its presence with a total of five authorizations (four peptides and one oligonucleotide). Interestingly, 23 out of 37 drugs were first-in-class and thus received fast-track designation by...

Peptides play an important role in many fields including immunology, medical diagnostics and drug discovery due to their high specificity and positive safety profile. However, for their delivery as active pharmaceutical ingredients, delivery vectors, or diagnostic imaging molecules, they suffer from two serious shortcomings; their poor metabolic st...

Peptides are gaining ground in the pharmaceutical arena, with a total of 22 approvals over the last six years. These molecules are also present in antibody-drug conjugate constructs as linkers or payloads, or both. Solid-phase peptide synthesis (SPPS) is the method of choice for peptide synthesis. The introduction of the automatic synthesizer has f...

Amino-Li-resin is a new and unique polyacrylamide resin presented in the form of fibers and is found to be well suited for solid-phase peptide chemistry. Although amino-Li-resin swells much better in polar solvents, it is also compatible with some non-polar solvents. It comes with a high loading of functional amino groups, thus maximizing its produ...

An immunochemical strategy to detect and quantify AIP-IV, the quorum sensing (QS) signaling molecule produced by Staphylococcus aureus agr type IV, is reported here for the first time. Theoretical calculations and molecular modeling studies have assisted on the design and synthesis of a suitable peptide hapten (AIPIVS), allowing to obtain high avid...

From the medical, pharmaceutical, and social perspectives, 2021 has been a year dominated by the COVID-19 pandemic. However, despite this global health crisis, the pharmaceutical industry has continued its endeavors, and 2021 could be considered an excellent year in terms of the drugs accepted by the US Food and Drug Administration (FDA). Thus, dur...

As one of the major therapeutic options for cancer treatment, chemotherapy has limited selectivity against cancer cells. Consequently, this therapeutic strategy offers a small therapeutic window with potentially high toxicity and thus limited efficacy of doses that can be tolerated by patients. Antibody-drug conjugates (ADCs) are an emerging class...

An in silico study, using the GALAS algorithm available in ACD/PhysChem Suite, was performed to calculate the pK a(s) of various oximes with potential application as peptide coupling additives. Among the known oximes and predicted structures, OxymaPure is superior based on the pK a values calculated, confirming the results described in the literatu...

Similar to last year, 2021 will be remembered for the COVID-19 pandemic. Although five vaccines have been approved by the two most important drug regulatory agencies, namely the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the pandemic has still not been brought under control. However, despite the context of a glob...

An in-silico study, using the GALAS algorithm available in ACD/Percepta, was performed to calculate the pK a (s) of the various oximes with potential application as peptide coupling additives. Among the known oximes and predicted structures, OxymaPure is superior based on the pK a values calculated, confirming the results described in the literatur...

N,N’-diisopropylcarbodiimide (DIC) and OxymaPure are the reagents of choice for the formation of peptide bonds in Solid-Phase Peptide Synthesis (SPPS). The combined use of DIC and OxymaPure in model cases can be accompanied by a serious side reaction with the ultimate formation of oxadiazole and HCN. Here we demonstrate, in a practical case, that t...

The administration and controlled release of drugs over time remains one of the greatest challenges of science today. In the nanomaterials field, anisotropic gold nanoparticles (AuNPs) with plasmon bands centered at the near-infrared region (NIR), such as gold nanorods (AuNRs) and gold nanoprisms (AuNPrs), under laser irradiation, locally increase...

Herein we describe a native mass spectromery protein-peptide model as a competent surrogate for the HOP–HSP90 Protein-Protein Interaction (PPI), application of which led to the qualititive identification of two new...

The development of methyl transverse relaxation optimized spectroscopy has greatly facilitated the study of macromolecular assemblies by solution NMR spectroscopy. However, limited sample solubility and stability has hindered application of this technique to ongoing studies of complexes formed on membranes by the neuronal SNAREs that mediate neurot...

Antimicrobial resistance is one of the most significant threats to health and economy around the globe and has been compounded by the emergence of COVID-19, raising important consequences for antimicrobial resistance development. Contrary to conventional targeting approaches , the use of biomimetic application via nanoparticles for enhanced cellula...

Peptide synthesis is an area with a wide field of application, from biomedicine to nanotechnology, that offers the option of simultaneously synthesizing a large number of sequences for the purpose of preliminary screening, which is a powerful tool. Nevertheless, standard protocols generate large volumes of solvent waste. Here, we present a protocol...

Hydroxypyridones (HOPOs) are an important class of chelating compounds. They bind strongly to hard metal ions such as Fe(III). Here we present the solid‐phase synthesis of peptides containing 1,2‐HOPO moieties linked through a carboxylic acid placed at position 4 of the ring. A total of four ligands were studied, two bidentate and two hexadentate....

Peptide ligands are widely used in protein purification by affinity chromatography. Here, we applied a fully automated two-stage library screening method that avoids false positive peptidyl-bead selection and applied it to tetanus toxoid purification. The first library screening was performed using only sulforhodamine (a fluorescent dye), and fluor...

PolarClean, a green solvent prepared through the valorization of a byproduct of Nylon-66 manufacturing, shows an excellent capacity to dissolve all Fmoc-amino acids and key coupling reagents and additives. It can also swell polystyrene and ChemMatrix, the two resins most widely used in solid-phase peptide synthesis. The synthesis of model peptides...

Peptides have a broad number of applications: from biochemical tools to diagnostic kits; from nanotechnology to new materials; and from vaccines to drugs [...]

Microbial infections are a major public health concern. Antimicrobial peptides (AMPs) have been demonstrated to be a plausible alternative to the current arsenal of drugs that has become inefficient due to multidrug resistance. Herein we describe a new AMP family, namely the super-cationic peptide dendrimers (SCPDs). Although all members of the ser...

DMB (Dimethylbarbituric) and DETB (Diethylthiobarbituric) are both barbituric and thiobarbituric acid derivatives respectively, that forms enamines with the Nα amine of amino acids. These compounds were found to be stable crystalline solids and show stability in the standard acidic and basic conditions used for solid‐phase peptide synthesis (SPPS)...

The development and use of nanosystems is an emerging strategy for the diagnosis and treatment of a broad number of diseases, such as Alzheimer's disease (AD). Here, we developed a neurotheranostic nanosystem based on gold nanorods (GNRs) that works as a therapeutic peptide delivery system and can be detected in vivo for microcomputed tomography (m...

High susceptibility to proteolytic degradation in the gastrointestinal tract limits the therapeutic application of peptide drugs in gastrointestinal disorders. Linaclotide is an orally administered peptide drug for the treatment of irritable bowel syndrome with constipation (IBS-C) and abdominal pain. Linaclotide is however degraded in the intestin...

The Front Cover shows a pictorial description of a H2@C60 hybrid molecule with a dehydroepiandrosterone moiety interacting with an enzyme receptor. This endohedral derivative can interact with the active site of SARS Cov‐2, as predicted by docking studies, and behaves as a potential protease inhibitor. More information can be found in the Full Pape...

Obesity and overweight are associated with lethal diseases. In this context, obese and overweight individuals infected by COVID-19 are at greater risk of dying. Obesity is treated by three main pharmaceutical approaches, namely suppressing appetite, reducing energy intake by impairing absorption, and increasing energy expenditure. Most compounds us...

Invited for this month's cover are the collaborating groups of Dr. Margarita Suárez at Universidad de La Habana, Cuba, and Dr. Nazario Martín at Universidad Complutense de Madrid, Spain, together with groups at other institutions worldwide. The Front Cover shows a representation of the H2@C60 hybrid molecule with a dehydroepiandrosterone moiety int...

Background In fish farming, the plant extracts containing antioxidant compounds have been added to the diet for enhancing pathogen resistance. In vitro studies evaluating the antioxidant effect of herbal extracts on fish cell models have been focused on ROS production and the respiratory burst mechanism. However, the effects on enzymatic antioxidan...

While the focus of industry was once to cover people’s needs, it is now imperative to address how to minimize or even stop generating waste, either by decreasing the amount produced or by recycling and reusing it in the same or another synthetic flow. The closed-loop strategy has gained ground in the context of global resource depletion. In this r...

The cover picture shows two scientists standing around the molecular structure of the coupling reagent T3P which is the pillar of the present study. The two scientists reflect the close partnership between the university UKZN and the company AMRI investigating T3P in the new application field Solid Phase Peptide Synthesis (SPPS). The green colour i...

Despite the active research towards introducing novel anticancer agents, the long-term sequelae and side effects of chemotherapy remain the major obstacle to achieving clinical success. Recent cancer research is now utilizing the medicinal chemistry toolbox to tailor novel ‘smart’ carrier systems that can reduce the major limitations of chemotherap...

Several derivatives containing morpholine/piperidine, anilines, and dipeptides as pending moieties were prepared using s-triazine as a scaffold. These compounds were evaluated for their anticancer activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293)...

2020 has been an extremely difficult and challenging year as a result of the COVID-19 pandemic and one in which most efforts have been channeled into tackling the global health crisis. The US Food and Drug Agency has ap-proved 53 new drug entities, six of which fall in the peptides and oligonucleotides (TIDES) category. The number of authorizations...

This review provides an overview of the broad applicability of s-triazine. Our many years working with this intriguing moiety allow us to discuss its wide activity spectrum (inhibition against MAO-A and -B, anticancer/antiproliferative and antimicrobial activity, antibacterial activity against MDR clinical isolates, antileishmanial agent, and use a...

Amidation is the predominant reaction within the pharmaceutical setting, and it is attracting greater attention due to the increased demand for therapeutic peptides. The high therapeutic efficacy and safety profile of peptides have placed these molecules in prime position within the pharmaceutical arena, which is reflected by these molecules receiv...

Vasopressin (VP) and oxytocin (OT) are cyclic neuropeptides that regulate fundamental physiological functions via four G protein-coupled receptors, V1aR, V1bR, V2R, and OTR. Ligand development remains challenging for these receptors due to complex structure–activity relationships. Here, we investigated dimerization as a strategy for developing liga...

Although the pharmaceutical industry will remember 2020 as the year of COVID-19, it is important to highlight that this year has been the second-best—together with 1996—in terms of the number of drugs accepted by the US Food and Drug Administration (FDA). Each of these two years witnessed the authorization of 53 drugs—a number surpassed only in 201...

As a contribution to the chemistry of H2@C60, here we report the synthesis and characterization of a novel hybrid containing a dehydroepiandrosterone moiety through a cyclopropanation reaction in a 76% yield. Theoretical calculations at DFT‐D3(BJ)/PBE 6‐311G(d,p) level predict the most stable conformation and that the saturation of a double bond is...

A novel small library of seven fluorinated quinazoline derivatives was synthesized and for four of them, the crystal structures were solved by single X-ray diffractometer and compared the confirmation of molecules in solution-phase using 2D NOESY experiments. Taking advantage of the series prepared, we were able to describe the influence of various...

PEPSTAR, a „rising star“ in peptide synthesis, features a „nanostar“ support to grow peptides with organic solvent nanofiltration for isolation. The three‐armed and monodisperse nanostar enables efficient nanofiltration and real‐time reaction monitoring. A cycle consists of coupling, Fmoc removal and nanofiltration, which all performed continuously...

Herein, a one‐pot liquid phase peptide synthesis featuring iterative addition of amino acids to a ‘nanostar’ support, with organic solvent nanofiltration (OSN) for isolation of the growing peptide after each synthesis cycle is reported. A cycle consists of coupling, Fmoc removal, then sieving out of the reaction by‐products via nanofiltration in a...

Using the classical Ugi four-component reaction to fuse an amine, ketone, carboxylic acid, and isocyanide, here we prepared a short library of N-alkylated α,α-dialkylglycine derivatives. Due to the polyfunctionality of the dipeptidic scaffold, this highly steric hindered system shows an interesting acidolytic cleavage of the C-terminal amide. In th...

Despite the progress in cancer nanotherapeutics, some obstacles still impede the success of nanocarriers and hinder their clinical translation. Low drug loading, premature drug release, off-target toxicity and multi-drug resistance are among the most difficult challenges. Lactoferrin (LF) has demonstrated a great tumor targeting capacity via its hi...

In this chapter, a protocol to design affinity chromatography matrices with short peptide ligands immobilized for protein purification is described. The first step consists of the synthesis of a combinatorial peptide library on the hydroxymethylbenzoyl (HMBA)-ChemMatrix resin by the divide–couple–recombine (DCR) method using the Fmoc chemistry. Nex...

Solid-phase peptide synthesis (SPPS) enables routine synthesis of virtually any type of peptide sequence and is the preferred method for peptide synthesis in academia and the pharmaceutical industry alike. Still,...

Significant efforts have been made in recent years to identify more environmentally benign and less hazardous alternatives to N,N-dimethylformamide (DMF) in solid-phase peptide synthesis (SPPS). Several greener solvents have been...

We have studied the diversity and specificity of interactions of amphibactin produced by Vibrio genus bacterium (Vibrio sp. HC0601C5) with iron and various metal ions in + 3 oxidation state in an octahedral (Oh) environment. To survive in the iron-deficient environment of their host, pathogenic bacteria have devised various efficient iron acquisiti...

A new series of thiobarbituric (thiopyrimidine trione) enamine derivatives and its analogues barbituric acid derivatives was synthesised, characterised, and screen for in vitro evaluation of α-glucosidase enzyme inhibition and anti-glycation activity. This series of compounds were found to inhibit α-glucosidase activity in a reversible mixed-type m...

After the Industrial Revolution, humanity began to exploit non-renewable resources, such as oil and gas, with dangerous consequences for the environment. In the last 50 years, different strategies have been implemented to reduce the environmental impact produced by the chemical and pharmaceutical industries. Biotechnology offers different perspecti...

Two new disulfide-based protecting groups (SIT and MOT) are proposed for Cys thiol in the substitution of StBu, which is often difficult to remove. Both groups are based on a secondary thiol with a branched point in the β-position for an efficient modulation of its lability and/or stability. This unique structure allows them to be fully compatible...

2,4,6-Trichloro-1,3,5-triazine (TCT) offers the unique ability to undergo sequential nucleophilic substitution reactions using regular nucleophiles (first Cl replacement at 0 °C, second at RT, and third at >90 °C), making s-triazine a privileged scaffold-finding application in drug development with an extension towards the development of new materi...

OxymaPure [ethyl 2-cyano-2-(hydroxyimino)acetate] is an exceptional reagent with which to suppress racemization and enhance coupling efficiency during amide bond formation. The tremendous popularity of OxymaPure has led to the development of several Oxyma-based reagents. OxymaPure and its derived reagents are widely used in solid- and solution-phas...

In the field of bioconjugation, linker development has witnessed massive growth in recent years. 2,4,6-Trichloro-1,3,5-triazine (TCT) is a tridentate linker that can accommodate three distinct nucleophiles. Herein, the reaction of azido triazine derivatives with nucleophiles (amine, thiol and phenol) is studied. The replacement of first chlorine wa...

A novel series of 4,6-disubstituted s-triazin-2-yl amino acid derivatives was prepared and characterized. Most of them showed antifungal activity against Candida albicans compared to clotrimazole (standard drug). Compounds bearing aniline derivatives, piperidine and glycine on the triazine core showed the highest inhibition zones at concentrations...

Ocellatins are a family of antimicrobial peptides found exclusively in the Leptodactylus genus. To date, 10 species have been studied and more than 23 peptides described. Here we report the sequences of five new peptides from the skin of the frog Leptodactylus latrans (Anura: Leptodactylidae) determined by cDNA cloning of the complete prepro-peptid...

Solid-phase peptide synthesis has become an important technique as the method of choice to deliver high quality peptide entities at both laboratory and production scale. The polymeric support (i.e. the resin) is the most essential part of the process as it covalently holds the growing peptide through the various synthetic steps. Several key feature...

Antimicrobial peptides (AMPs) have the ability to penetrate as well as transport cargo across bacterial cell membranes, and they have been labeled as exceptional candidates to function in drug delivery. The aim of this study was to investigate the effectiveness of novel formulation of AMPs for enhanced MRSA activity. The strategy was carried out th...

•Metal chelation has found many applications that directly affect human's life.•Natural siderophores are one of the most potent chelators for Fe (III)•1-Hydroxypyridine-2-one (1,2-HOPO) (Fig. 1a), which is shown in 4-carboxy-1-hydroxypyridin-2-one (1,2-HOPO-4-COOH) (Fig. 1b), is a moiety that electronically resembles the hydroxamate group found in...

Hydroxamic acids are an important class of molecules, in particular because of their metal-chelating ability. Microorganisms, including pathogenic bacteria, use hydroxamate-based entities (siderophores), among others, to acquire Fe (III). The “Trojan horse” strategy exploits the need of bacteria for this metal by using Fe (III) active transporters...

Several factors have influenced the increasing presence of peptides as an important class of Active Pharmaceutical Ingredients. One is the continued development of synthetic methodologies for peptide synthesis. Herein, we investigated the Fmoc removal step, using the tea-bag strategy. In this regard, three different secondary amines: piperidine, 4-...

En este contexto nace REDIPEPT (Figura 2) , la Red Iberoamericana de Péptidos Terapéuticos, cuyo objetivo fundamental es crear y fortalecer vínculos de colaboración entre grupos iberoamericanos que desarrollan investigación focalizada en la búsqueda, identificación, diseño y síntesis de péptidos y derivados con potencial terapéutico. Los temas de i...

E n estos días donde la mayoría de nuestros países se encuentran haciendo frente a la pandemia desenca-denada por el COVID-19, podemos leer en los medios de comunicación que la Plitidepsin (Aplidin®) de la biotecnológica española PharmaMar ha demostrado in vivo una potencia entre 80 y 2.800 veces superior 1 , según el tipo de célula, al Remdesivir®...

Finding alternatives to gadolinium (Gd)-based contrast agents (CA) with the same or even better paramagnetic properties is crucial to overcome their established toxicity. Herein we describe the synthesis and characterization of entirely organic metal-free paramagnetic macromolecules based on biocompatible oligoethylene glycol dendrimers fully funct...