700 Protein & Peptide Letters, 2012, 19, 700-707
1875-5305/12 $58.00+.00 © 2012 Bentham Science Publishers
Bioactive Peptides from Marine Organisms: A Short Overview
Fernando Lazcano-Pérez, Sergio A. Román-González, Nuria Sánchez-Puig* and Roberto Arreguín-
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, México
04510, D.F., México
Abstract: Marine organisms are an immense source of new biologically active compounds. These compounds are unique
because the aqueous environment requires a high demand of specific and potent bioactive molecules. Diverse peptides
with a wide range of biological activities have been discovered, including antimicrobial, antitumoral, and antiviral activi-
ties and toxins amongst others. These proteins have been isolated from different phyla such as Porifera, Cnidaria, Nemer-
tina, Crustacea, Mollusca, Echinodermata and Craniata. Purification techniques used to isolate these peptides include clas-
sical chromatographic methods such as gel filtration, ionic exchange and reverse-phase HPLC. Multiple in vivo and in vi-
tro bioassays are coupled to the purification process to search for the biological activity of interest. The growing interest
to study marine natural products results from the discovery of novel pharmacological tools including potent anticancer
drugs now in clinical trials. This review presents examples of interesting peptides obtained from different marine organ-
isms that have medical relevance. It also presents some of the common methods used to isolate and characterize them.
Keywords: Marine toxins, reverse-phase HPLC, peptides, chromatography.
and more than 90% of all living classes of organisms are
found in the marine environment. In addition, the oceans
cover more than 70% of the Earth’s surface and thus consti-
tute an enormous wealth of natural products and new bio-
logically active compounds . The chemical structure of
these compounds is very different from those obtained from
terrestrial and microbial systems. It is possible to find cyclic
and linear peptides and depsipetides (peptides in which one
or more of the amide bonds are replaced by ester bonds) con-
taining natural or non-natural amino acids (Figure 1). These
molecules can be synthesized by the organism itself or can
be obtained from marine microorganisms with whom they
have a symbiotic relationship . Sessile marine inverte-
brates have evolved sophisticated chemical mechanisms that
they use for communication, defense, reproduction, and
regulation of calcium and sodium homeostasis or as antimi-
crobial agents. Their value as drugs is based on the fact that
they interact with proteins that have been conserved
throughout evolution and some of their human orthologues
may be involved in human disease processes, e.g., cell divi-
sion and apoptosis, or immune and inflammatory responses.
Several biological and pharmacological activities have been
reported for molecules isolated from marine species that
comprise antitumoral, antibacterial, antifungal, antiviral,
immunosuppressive, insecticidal, neurotoxic and cytotoxic
properties. The type of organisms from which these active
compounds have been isolated includes marine invertebrates
Marine biodiversity is so vast that the majority of phyla
*Address correspondence to this author at the Instituto de Química, Univer-
sidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universi-
taria, México 04510, D.F., México; Tel: +52 55 56224468; Fax: +52 55
56162217; E-mail: firstname.lastname@example.org
Figure 1. Chemical structure of the Mirabamide-G depsipeptide
from the marine sponge Stelletta clavosa . Ester bond charac-
teristic of a depsipeptide and other interesting chemical features
such as the non-natural amino acids present in this compound are
highlighted as follow: Cyan: 2,3-dihydroxy-2,6,8-trimethyldeca-
(4Z,6E)-dienoic acid (Dhtda) moiety, dark blue: 2,3 diamino buta-
noic acid (Dab), brown: 3-hydroxyleucine, pink: N-methylthreo-
nine, green: ???????????????????, yellow: ??????????????????
???????? ??????????????????? ?????? ??????????????????????? ????
Bioactive Peptides from Marine Organisms Protein & Peptide Letters, 2012, Vol. 19, No. 7 701
such as sponges, mollusks, sea anemones, tunicates, poly-
chaetes, echiuroid worms, crustaceans and to a lesser extent
from fish .
follow for the isolation and characterization of a bioactive
substance: (a) the source selection, (b) extraction and frac-
tionation, (c) separation and isolation of the molecules of
interest and (d) the structural and functional characterization.
Peptides from animal tissues must be efficiently solubilized
in their biologically active form and recovered in high yields
avoiding a rapid degradation. The extraction of marine pep-
tides and proteins of interest from their natural source is usu-
ally made in water or aqueous buffers in order to maintain
their functionality. Fractionation is often done using a salt
(e.g. ammonium sulfate) or acetone. The purification steps
usually include chromatographic methods like gel filtration,
ion exchange and reverse-phase high performance liquid
chromatography (RP-HPLC). This last being the method of
choice for the purification of peptides from their natural
sources . Finally, techniques like Edman degradation or
protease digestion followed by mass spectrometry are used
to identify the primary sequence of the peptide, while circu-
lar dichroism and NMR provide information related to their
secondary and tertiary structure respectively.
According to Cannell , there are five main steps to
it is very important to have a sensitive and reproducible se-
lection system that allows the experimenter the identification
of the peptide of interest . A good selection system is the
key to find new biologically active compounds that can be
used as pharmacological tools for elucidating physiological
mechanisms and new therapeutic agents. The biological as-
says used to follow the activity of the different fractions ob-
tained during the purification steps include a wide range of
in vivo and in vitro experiments like hemolysis, citotoxicity,
antimicrobial, antitumoral and antiviral activities and elec-
Before starting the isolation of novel bioactive molecules
pounds is not generally known, nor how the host organism
produces them. This makes difficult finding an application
for them, but their evaluation in nontraditional disease tar-
gets (i.e., other than cancer, inflammation, and infectious
diseases) could lead to the discovery of novel drugs.
The native function of the different marine-derived com-
PEPTIDES FROM SEA SPONGES
bioactive peptides. Structurally, they include linear peptides,
peptide lactones, cyclic peptides, and depsipeptides (a grow-
ing research area in several cancer cell lines ). Some of
these depsipeptides contain non-proteinogenic amino acids
or hydroxy acid residues, while others show minimal altera-
tions from the common ribosomal peptides. Cyclodepsipep-
tides produced by marine sponges have unique structures
that comprise unusual amino acids and N-terminal
polyketide-derived moieties . However, it is rather diffi-
cult to isolate sufficient quantities of these metabolites for
pharmacological and toxicological testing . Papuamides
are a representative class of marine sponge cyclic depsipep-
tides. Papuamide A was isolated from Theonella mirabilis
and T. swinhoei and protected T-acute lymphoblastic leuke-
mia cell cultures from infection by HIV . Homo-
Sea sponges are a well-known source of interesting new
phymines, B–E and A1–E1 were isolated from the sponge
Homophymia sp. and elicited a potent cytotoxic activity with
IC50 values in the nM range against a variety of human can-
cer cell lines .
Stylopeptide 2 is a proline-rich cyclodecapeptide that has
been isolated from a cytotoxic extract of the Papua New
Guinea marine sponge Stylotella sp. The structural assign-
ment was based on Collision Induced Dissociation (CID),
NMR spectroscopy and amino acid analysis. This peptide
was initially purified from a dichloromethane-methanol ex-
tract by solvent partitioning. The dichloromethane-soluble
fraction that contained the stylopeptide 2 displayed activity
against the P388 lymphocytic leukemia cells. Successive
Sephadex LH-20 partition chromatography followed by vac-
uum-liquid chromatography, preparative thin-layer chroma-
tography (TLC), and high-performance liquid chromatogra-
phy (HPLC) rendered the pure compound .
been isolated from the Puerto Rican marine sponge Pro-
suberites laughlini. The structures were elucidated by
chemical degradation, ESI MS/MS and extensive 2D NMR
methods . To purify these peptides, the sample was ini-
tially fractionated with ethyl acetate followed by 1H and 13C
NMR to confirm the presence of peptides. The extract was
further subjected to normal-phase Silica gel column chroma-
tography using a mixture of chloroform and methanol previ-
ously saturated with NH3. Similar fractions were pooled to-
gether based on their TLC, NMR, and biological activity
profiles. The first fraction contained a mixture of small pep-
tides that were further fractionated using a silica gel column
chromatography with a mixture of hexane and ethyl acetate.
Further purification of one the fractions by C-18 Silica gel
reverse-phase chromatography yielded pure euryjanicin A,
euryjanicin B, and the known cyclic octapeptide Dominicin.
Pure euryjanicin C and D were obtained by subsequent re-
Three cyclic peptides, euryjanicins B, C and D, have
and B were isolated from the marine sponge Ceratopsion sp.
They are linear peptides rich in dehydroamino acids and ?-
hydroxyamino acids with an inhibitory growth effect against
several human cancer cell lines .
Recently two cytotoxic peptides named Yaku’amides A
isolated from a deep-water marine sponge Theonella swin-
hoei. The methanol extract of the lyophilized sponge was
partitioned between butanol and water and the organic layer
was fractionated on Sephadex LH-20. Fractions containing
peptides were purified by reverse-phase HPLC. The struc-
tures of paltolides A-C were determined by NMR and tan-
dem MS techniques and belong to a rare subgroup of
sponge-derived anabaenopeptins that have in common a C-
terminal tryptophan residue linked to the epsilon-amine of a
lysine bearing a D-configuration .
New anabaenopeptin-like peptides, paltolides A-C, were
PEPTIDES FROM MOLLUSKS
lusks. Dolastatins are a group of cyclic and linear peptides
isolated from the sea hare Dollabella auricularia. Dolastatin
10 is a linear peptide with antitumoral activity against mur-
ine leukemia P388 cells. It displayed unprecedented potency
Cytotoxic cyclic peptides have also been found in mol-
702 Protein & Peptide Letters, 2012, Vol. 19, No. 7 Lazcano-Pérez et al.
in experimental antineoplastic and tubulin assembly systems.
It is in Phase I clinical trials as anticancer agent for treatment
of breast and liver cancers, solid tumors and leukemia .
Kahalalide F is a cyclic depsipeptide discovered in the slug
Elysia rufescens that showed in vitro and in vivo selectivity
for prostate-derived cell lines and tumors. This peptide is in
phase I clinical trials in patients with androgen-independent
prostate cancer . Conus mollusks contain a family of
linear peptides rich in disulfide bonds known as conotoxins.
The Conus Genus
comprising 500 to 700 different species [18, 19]. They can
be divided in three groups according to their feeding habits:
piscivorous (fish eaters), vermivorous (worm eaters) and
molluscivorous (mollusk eaters). They use a complex mix-
ture of biological active molecules for functions such as de-
fense against predators, paralyzing their prey to eat it or to
repel another competing cone for the same ecological niche.
Conus toxins (or conotoxins) are short peptides (8-50 amino
acids) rich in cysteines. These conopeptides are organized in
Superfamilies that originate from a handful of genes .
Until now there have been described 13 superfamilies named
by capital letters. Additionally, each conopeptide is further
classified in families described by a Greek letter according to
their pharmacological target . The sequence of each
toxin is highly variable and the only conserved region within
a superfamily corresponds to that of the cystine framework
. The framework is defined according to the cysteine
arrangement along their sequence and, in some cases, ac-
cording to their disulfide connectivity (Figure 2) .
The marine cone snails are a diverse group of animals
Conotoxins Molecular Targets
ion channels, transporters and membrane receptors .
They affect the ion influx and outflow passing through the
cell membrane. This in turn, results in the depolarization of
The conotoxins affect the mechanism of action of many
neural and muscular cells with subsequent paralysis of the
organism. The principal targets of these toxins are sodium
channels (?-, μ- and μO-conotoxins), potassium channels (?-
and ?A-conotoxins) , calcium channels (?-conotoxins),
nicotinic acetylcholine receptors (?-conotoxins) , nore-
pinephrine transporter inhibitors (?-conotoxins), and antago-
nist of nicotinic acetylcholine receptors (?-conotoxins) [20,
25, 26]. Most of the conotoxins have post-translational modi-
fications (PTMs) such as glycosylation, tryptophan broma-
tion, C-terminus amidation, glutamic acid ?-carboxylation,
N-terminal glutamine cyclization and tyrosine sulfation 
(Table 1). Mass-spectrometry is widely used to assess the
different post-translational modifications present in the cono-
toxins. The importance, however, of these modifications for
the toxins function is not clear yet. In some cases, synthetic
conopeptides lacking the native modifications are less active
or totally loose their activity , while other conopeptides
do not loose their activity at all . In addition, the precise
mode of interaction between the post-translational modifica-
tion and the molecular target has not been yet elucidated. It
has been suggested that the similarities between the structure
of serotonin with that of the bromotryptophan residue pre-
sent in ?-conotoxins could explain the activity of this peptide
against the serotonin receptor . Due to their potency in
blocking ion-channels, conotoxins could be used to treat
pathologies related to the malfunctioning of these channels.
Ziconotide (Prialt™) is one of the few conotoxins approved
for medical use [31-33]. It is a synthetic drug derived from
the ?-conotoxin M-VII-A of Conus magus that acts as a cal-
cium antagonist and is used to treat chronic pain. Its analge-
sic effect is 1000 more potent than morphine with the advan-
tage of not being addictive [34, 35].
venom duct of the animal and macerate it in a buffered solu-
tion to extract all the peptides present in it. Removal of the
venom duct means the death of the animal, reason why many
scientists around the world use “milking” of these animals
To isolate conus toxins it is necessary to first remove the
Figure 2. Schematic organization of Conus peptides rich in disulfide bonds depicting the gene superfamilies, cysteine arrangement and
pharmacological targets. A detailed list of the superfamilies and frameworks can be review in data deposited in the ConoServer. ? – unknown
Bioactive Peptides from Marine Organisms Protein & Peptide Letters, 2012, Vol. 19, No. 7 703
instead. In this technique the animal is incited to expel its
harpoon into a latex membrane where the toxins are col-
lected [30, 36]. Subsequently the mixture is fractionated by
RP-HPLC in a C-18 column and the peptides eluted with a
linear gradient of acetonitrile, water and TFA [37-40]. The
peptides obtained from the fractionated venom are analyzed
by mass spectrometry. This technique gives basic informa-
tion regarding the primary sequence, the post-translational
modifications and even the cysteine pairing of known toxins
. Analysis of the conotoxin genes is not easy due to the
low sequence conservation amongst them. To facilitate the
classification of conotoxins, a specialized database named
“ConoServer” (www.conoserver.com) was built. This data-
base contains the nucleotide sequences of the different genes
that codify for the conotoxins together with the correspond-
ing primary sequence of the prepropeptides and mature pep-
tides. This program allows the comparison of any new se-
quence with those contained in the database using a Blast
program to identify the superfamily of the toxin and its prob-
able pharmacological effect .
its members are toxic. Cnidarian toxins are a rich source of
polypeptides with a wide variety of biological activities such
as pore-forming cytolisins, phopholipases, neurotoxins and
protease inhibitors. Sea anemones have been extensively
studied compared to other cnidarians due to the stability of
their toxins . These toxins selectively target ion channels
and provide potent molecular probes for ion channel struc-
ture and function .
The phylum Cnidaria is unique such that practically all of
Sea Anemones Toxins
nel toxins, potassium channel toxins, acid-sensing ion chan-
nel toxins and protease inhibitors. The first cnidarian Na+
channel modulating toxins purified were ATXs I-III from
Anemonia sulcata  and Anthopleurin A from An-
thopleura xanthogrammica . Sodium channel toxins are
subdivided into four types: type 1 and 2 toxins contain 46-49
amino acids, except for AeI from Actinia equina that is 54
amino acid long, and all of them possess three disulfide
bridges. Type 3 toxins consist of 27-32 amino acid residues
and may have three or four disulfide bridges. Type 4 toxins
include Calitoxin I and Calitoxin II that were isolated from
Calliactis parasitica and are constituted by 46 amino acid
residues and three disulfide bridges.
The first purified K+ channel blocker was BgK from
Bunodosoma granulifera . Since then, the pharmacologi-
cal properties and chemical structure of other sea anemones
have been described [46-50]. Potassium channel toxins have
been classified into three types: type 1 toxins block Kv1
(Shaker) potassium channels. They have 35-37 amino acid
residues and are cross-linked by three disulfide bridges. Type
2 toxins, known as Kalicludines 1-3 (AsKC), have 58-59
amino acid residues and also exhibit blocking activity
against Kv1 potassium channels though with less potency
than type 1 toxins. AsKC 1, 2 and 3 share sequence identity
with Kunitz-type protease inhibitors so they also act as pro-
tease inhibitors. Type 3 toxins are represented by BDS-I and
BDS-II from Anemonia sulcata that specifically block Kv3.4
channels and APETx1 from Anthopleura elegantissima a
selective blocker of human ether-a-go-go-related gene
Sea anemone neurotoxins are divided into sodium chan-
Table 1. Common Post-translational Modifications Present in Conotoxins and the Enzymes Responsible for it
Modification Peptide Sequence Enzyme Reference
Disulfide bond formation GI
Hydroxylation of proline GIIIA RDCCTOOKKCKDRQCKOQRCCA^ Proline hydroxylase 
Hydroxylation of D-valine gld-V* APANS(dHyV)WS
Hydroxylase with D-
amino acid specificity
Amidation of C-terminus SI ICCNPACGPKYSC^
Carboxylation of glutamic acid Conantokin-G GE??LQVNQ?LIR?KSN^
?-Glutamate carboxylase 
Bromination of tryptophan Bromocontryphan GCOwEPW†C^ Bromo peroxidase 
Isomerization of tryptophan Contryphan GCOwEPWC^ Tryptophan epimerase 
Cyclization of N-terminal Gln Tx10c
ZTCCGYRMCVOC^ Glutaminyl cyclase 
Sulfation of tyrosine EpI GCCSDPRCNMNNPY‡C^ Tyrosyl sulfotranferase 
?, ?-carboxyglutamate; Z, piroglutamic acid; Y‡, tyrosine sulfate; w, D-tryptophan; W†, 6-L-bromotryptophan; O, 4-trans hydroxyproline; S§, Hex3HexNAc2-Ser; ^ indicates ami-
dated C-terminus; dHyV, D-?-hydroxyvaline.
704 Protein & Peptide Letters, 2012, Vol. 19, No. 7 Lazcano-Pérez et al.
(HERG) potassium channels. APETx1 inhibits human
HERG channel currents in a voltage-dependent manner by
shifting the activation properties of HERG channel . An
inhibitor of an acid-sensing ion channel, APETx2, has been
isolated from Anthopleura elegantissima . It inhibits
only the ASIC-3 channel making it a promising tool to study
the physiological involvement of it in neuronal excitability
and pain coding.
channel toxins from sea anemones use traditional chroma-
tographic methods. The first step generally uses a size exclu-
sion chromatography with a small pore resin such as Se-
phadex G-50  combined in some cases with the use of a
Serdolit® AD-2 column after an acetone precipitation of the
proteins [52, 53]. Gel filtration is usually followed by a
cation exchange chromatography and a final purification by
RP-HPLC. Recently, four toxins toxic to crabs were purified
from the whole body extract of Stichodactyla haddoni using
just two steps, a gel filtration on Sephadex G50 and RP-
HPLC . Two of these toxins are new structurally potas-
sium channel toxins different from those already reported
such that they are cross-linked by two disulfide bridges. The
only other sea anemone toxin with two disulfide bridges is
AmI from A. maculata that has four cysteine residues at the
same positions as SHTX I and SHTX II .
The methods used for the isolation of several sodium
mately 45 kDa have been isolated from the jellyfish Caryb-
dea rastoni (CrTX-A and CrTX-B) and Carybdea alata
(CaTX-A and CaTX-B) [56, 57]. The four toxins were iso-
lated from the sonicated tentacles of the jellyfish. The hemo-
lysin CARTOX from Carybdea marsupialis with an appar-
ent molecular mass of about 102-107 kDa, was isolated ap-
plying the crude extract to a cellulose column . Sánchez-
Rodríguez and collaborators partially purified a neurotoxin
and three cytolysins from the same species using classical
Hemolytic toxins with molecular weights of approxi-
Chironex fleckeri were isolated from the nematocyst extract
by SDS-PAGE, then transferred to PVDF membranes and
stained with Coomassie R-250. Protein bands (43 and 45
kDa) were excised from the membranes, air-dried and ana-
lyzed by Edman degradation .
Two homologous proteins from the highly toxic sea wasp
BIOACTIVE PEPTIDES FROM CHELICERATA AND
biologically active substances including antimicrobial pep-
tides. These molecules have low molecular weights (less
than 10 kDa) and generally form pores in membranes .
These peptides have an amphipathic structure that facilitates
their ability to attach to, destabilize and/or penetrate the cy-
toplasmic membrane of microorganisms. The horseshoe crab
Lymulus polyphemus is the source of polyphemusins I and II,
two 18 residue peptides that inhibit the growth of Gram-
negative and Gram-positive bacteria and fungi. The hemo-
lymph of Thalamita crenata and Charybdis lucifera also
contain peptides with antimicrobial activity [61, 62]. A
proline and arginine-rich anti-microbial peptide of 37 amino
The hemolymph of marine invertebrates contains many
acids was isolated and characterized from the hemocytes of
the spider crab Hyas araneus. The peptide named Arasin 1
has an N-terminal domain rich in proline and arginine and a
C-terminal domain containing two disulfide bonds .
poisonings compared to other marine animals like coelenter-
ates, some species have been studied for their toxicological
and pharmacological interest . Sea urchin toxins have
been poorly studied, though some authors have isolated some
toxins from pedicellariae; the venomous apparatus in sea
urchins [65-67]. Recently, two antibacterial peptides were
isolated from coelomocyte extracts of Strongylocentrotus
Although echinoderms cause fewer envenomations and
toxic organism, which inflicts noxious symptoms due to the
venomous spines on its surface. An anticoagulant factor
named Plancinin was isolated from the crude venom of the
spines. The venom was fractionated with ammonium sulfate
and then applied into a DEAE-cellulose column. The pure
protein was obtained by using a Sephadex G50 column
twice. Plancinin is a dimeric peptide linked by a disulfide
bond of about 7500 Da in its native form . Two phos-
pholipases (named AP-PLA2-I and II) with hemolytic activ-
ity in the presence of phosphatidylcholine were purified from
the same starfish venom . These toxins were purified
using several techniques that included a CM-cellulose col-
umn followed by an ammonium sulfate precipitation, a
phenyl sepharose CL-4B column and a sephacryl S-200 col-
umn were used for toxin I, while a Superose 12 HR10/30
column was used for toxin II. Both purified toxins were fi-
nally achieved by RP-HPLC chromatography. The molecular
masses of native AP-PLA2-I and II were determined to be 28
and 12 kDa, respectively. Both PLA2s gave a single band
corresponding to a molecular mass of 15 kDa on SDS-PAGE
in the presence of a reducing agent indicating that AP-PLA2-
I is a dimer composed of the same subunit, while AP-PLA2-
II is a monomer. Shiomi et al.  purified a basic glycopro-
tein of 25 kDa determined by SDS disc electrophoresis using
CM-cellulose and Sephadex G-100 chromatography.
The crown-of-thorns starfish Acanthaster planci is a
PEPTIDES FROM NEMERTINES, ECHIUROIDS AND
lacteus contains a family of polypeptide cytotoxins (A-I, A-
II, A-III and A-IV) and neurotoxins (B-I, B-II, B-III and B-
IV) . To purify the A toxins, a Sephadex G-50 chroma-
tography followed by CM-cellulose gradient chromatogra-
phy was used. Two CM-cellulose gradient separations at
different pH values were required to resolve cytolisins A-III
and A-IV. As for the B toxins , the mucus was extracted
in acidic conditions and the toxic components were adsorbed
in a carboxymethylcellulose resin for storage. Desorption
was accomplished by packing the CM-cellulose in a column
and the components stepwise eluted with 0.1 M ammonium
acetate (pH 6.5) buffer. The first purification step was a Se-
phadex G-50F column chromatography. The third fraction
contained toxins lethal to crayfish and it was separated by
CM-cellulose gradient chromatography at pH 7.5.
The mucus secreted by the marine worm Cerebratulus
Bioactive Peptides from Marine Organisms Protein & Peptide Letters, 2012, Vol. 19, No. 7 705
crobial peptides, arenicin-1 and -2, from the marine poly-
chaeta’s Arenicola marina coelomocytes . The two pep-
tides exhibited activity against Gram-positive and Gram-
negative bacteria and fungi. The extract obtained from the
isolated coelomocytes was ultra-filtered and applied to a
preparative continuous acid-urea PAG electrophoresis and
the active fractions were purified by reverse-phase HPLC on
a C-18 column.
Ovchinnikova and co-workers purified two novel antimi-
worm Urechis unicinctus has been recently purified and
A novel anticoagulant peptide from the marine echiuroid
BIOACTIVE PEPTIDES FROM MARINE FISHES
source of peptides and proteins with biological activity. Fish
have an immune system that helps them to eliminate patho-
genic bacteria before they enter their skin barrier. Few an-
timicrobial peptides have been identified in fish , such an
example is an antimicrobial peptide found in the skin mu-
cous secretions of the winter flounder (Pleuronectes ameri-
Diverse marine fish species produce antifreeze polypep-
tides as a defense mechanism against freezing in cold sea-
water habitats. Type I and IV anti-freezing proteins have
been isolated form the skin of the longhorn sculpin
(Myoxocephalus octodecemspinosus) . Other anti-
freezing proteins have been isolated and partially character-
ized from skin tissues of the Atlantic snailfish, Liparis atlan-
ticus, and the cunner Tautogolabrus adspersus .
Marine vertebrates have not been extensively studied as a
have been isolated from the gills of red sea bream Chrys-
ophrys major . Peptide sequences were determined by a
combination of Edman degradation, mass-spectrometry and
HPLC analysis of the native peptides. The peptides named
chrysophsin-1, chrysophsin-2, and chrysophsin-3 consist of
20-25 amino acids. They are highly cationic and contain an
unusual C-terminal Arg-Arg-Arg-His sequence. The ?-
helical structures of the chrysophsin peptides were predicted
from their secondary structures and were confirmed by CD
Three isoforms of a novel C-terminally amidated peptide
ment resulted in the production of special peptides by marine
organisms for use in their immune systems, as anti-freezing
proteins or for defense and prey capture. In some other cases,
the native function of these peptides is not known, but most
of them display a variety of pharmacological effects. Many
of these compounds have been useful in medical research for
the design of novel potent and specific therapeutic agents for
human diseases. Compared to the terrestrial organisms, ma-
rine counterparts have not been extensively studied and more
than half of marine species have not yet been studied for the
production of new molecules of pharmacological interest.
Thus marine organisms represent a gold mine for drug dis-
Millions of years of evolution in a competitive environ-
DGAPA project PAPIIT IN204010. R. A-E acknowledges
the financial support from UNAM-DGAPA project PAPIIT
N. S-P acknowledges the financial support from UNAM-
 de Vries, D.J.; McCauley, R.D.; Walker, F. Identification of marine
organism extracts active at the EGF binding site of human A431
cells. Toxicon, 1994, 32(5), 553-559.
Aneiros, A.; Garateix, A. Bioactive peptides from marine sources:
pharmacological properties and isolation procedures. J. Chroma-
togr. B Anal. Technol. Biomed. Life Sci., 2004, 803(1), 41-53.
Haefner, B. Drugs from the deep: marine natural products as drug
candidates. Drug Discov. Today, 2003, 8(12), 536-544.
Cannell, R.J.P. How to approach the isolation of a natural product.
In: Natural Products Isolation, 1st ed.; Biotechnology, M.i., Ed.;
Humana Press: New Jersey, 1998; Vol. 4, pp. 1-51.
Conlon, J.M. Purification of naturally occurring peptides by re-
versed-phase HPLC. Nat. Protoc., 2007, 2(1), 191-197.
Shaw, C. Reverse-phase HPLC purification of peptides from natu-
ral sources for structural analysis. Methods Mol. Biol., 1997, 64,
Zhang, W.; Ding, N.; Li, Y. Synthesis and bioologycal evaluation
of analogues of teh marine cyclic depsipeptide obynamide. J. Pept.
Sci., 2011, 17, 533-539.
Matsunaga, S.; Fusetani, N. Nonribosomal peptides from marine
sponges. Curr. Org. Chem., 2003, 7(10), 945-966.
Andavan, G.S.B.; Lemmens-Gruber, R. Cyclodepsipeptides from
Marine Sponges: Natural Agents for Drug Research. Marine
Drugs, 8(3), 810-834.
Ford, P.W.; Gustafson, K.R.; McKee, T.C.; Shigematsu, N.; Mau-
rizi, L.K.; Pannell, L.K.; Williams, D.E.; de Silva, E.D.; Lassota,
P.; Allen, T.M.; Van Soest, R.; Andersen, R.J.; Boyd, M.R.
Papuamides A-D, HIV-inhibitory and cytotoxic depsipeptides from
the sponges Theonella mirabilis and Theonella swinhoei collected
in Papua New Guinea. J. Am. Chem. Soc., 1999, 121(25), 5899-
Zampella, A.; Sepe, V.; Bellotta, F.; Luciano, P.; D'Auria, M.V.;
Cresteil, T.; Debitus, C.; Petek, S.; Poupat, C.; Ahond, A. Homo-
phymines B-E and A1-E1, a family of bioactive cyclodepsipeptides
from the sponge Homophymia sp. Org. Biomol. Chem., 2009,
Brennan, M.R.; Costello, C.E.; Maleknia, S.D.; Pettit, G.R.; Erick-
son, K.L. Stylopeptide 2, a proline-rich cyclodecapeptide from the
sponge Stylotella sp. J. Nat. Prod., 2008, 71(3), 453-456.
Vera, B.; Vicente, J.; Rodriguez, A.D. Isolation and structural
elucidation of euryjanicins B-D, proline-containing cycloheptapep-
tides from the Caribbean marine sponge Prosuberites laughlini. J.
Nat. Prod., 2009, 72(9), 1555-1562.
Ueoka, R.; Ise, Y.; Ohtsuka, S.; Okada, S.; Yamori, T.; Matsunaga,
S. Yaku'amides A and B, cytotoxic linear peptides rich in dehy-
droamino acids from the marine sponge Ceratopsion sp. J. Am.
Chem. Soc., 2010, 132(50), 17692-17694.
Plaza, A.; Keffer, J.L.; Lloyd, J.R.; Colin, P.L.; Bewley, C.A.
Paltolides A-C, anabaenopeptin-type peptides from the palau
sponge Theonella swinhoei. J. Nat. Prod., 2010, 73(3), 485-488.
Yamada, K.; Okija, M.; Kigoshi, H.; Suenaga, K. Cytotoxic Sub-
stances from Opisthobranch Molluscs. In: Drugs from the sea;
Fusetani, N., Ed.; S. Karger, AG: Basel, 2000, 59-73.
Kijjoa, A.; Sawangwong, P. Drugs and cosmetics from the sea.
Mar. drugs, 2004, 2, 73-82.
Buczek, O.; Bulaj, G.; Olivera, B.M. Conotoxins and the posttrans-
lational modification of secreted gene products. Cell Mol. Life Sci.,
2005, 62(24), 3067-3079.
Olivera, B.M. E.E. Just Lecture, 1996. Conus venom peptides,
receptor and ion channel targets, and drug design: 50 million years
of neuropharmacology. Mol. Biol. Cell, 1997, 8(11), 2101-2109.
Norton, R.S.; Olivera, B.M. Conotoxins down under. Toxicon,
2006, 48(7), 780-798.
Kaas, Q.; Westermann, J.C.; Craik, D.J. Conopeptide characteriza-
tion and classifications: an analysis using ConoServer. Toxicon,
2010, 55(8), 1491-1509.
706 Protein & Peptide Letters, 2012, Vol. 19, No. 7 Lazcano-Pérez et al.
 Wang, C.Z.; Chi, C.W. Conus peptides--a rich pharmaceutical
treasure. Acta Biochim. Biophys. Sin. (Shanghai), 2004, 36(11),
Brinkman, D.; Burnell, J. Identification, cloning and sequencing of
two major venom proteins from the box jellyfish, Chironex fleck-
eri. Toxicon, 2007, 50(6), 850-860.
Chen, P.; Dendorfer, A.; Finol-Urdaneta, R.K.; Terlau, H.; Olivera,
B.M. Biochemical characterization of kappaM-RIIIJ, a Kv1.2
channel blocker: evaluation of cardioprotective effects of kappaM-
conotoxins. J. Biol. Chem., 2010, 285(20), 14882-14889.
Becker, S.; Terlau, H. Toxins from cone snails: properties, applica-
tions and biotechnological production. Appl. Microbiol. Biotech-
nol., 2008, 79(1), 1-9.
Kauferstein, S.; Kendel, Y.; Nicke, A.; Coronas, F.I.; Possani,
L.D.; Favreau, P.; Krizaj, I.; Wunder, C.; Kauert, G.; Mebs, D.
New conopeptides of the D-superfamily selectively inhibiting neu-
ronal nicotinic acetylcholine receptors. Toxicon, 2009, 54(3), 295-
Bowersox, S.S.; Luther, R. Pharmacotherapeutic potential of
omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium
channel blocker found in the venom of Conus magus. Toxicon,
1998, 36(11), 1651-1658.
Buczek, O.; Yoshikami, D.; Watkins, M.; Bulaj, G.; Jimenez, E.C.;
Olivera, B.M. Characterization of D-amino-acid-containing excita-
tory conotoxins and redefinition of the I-conotoxin superfamily.
FEBS J., 2005, 272(16), 4178-4188.
Bulaj, G.; Buczek, O.; Goodsell, I.; Jimenez, E.C.; Kranski, J.;
Nielsen, J.S.; Garrett, J.E.; Olivera, B.M. Efficient oxidative fold-
ing of conotoxins and the radiation of venomous cone snails. Proc.
Natl. Acad. Sci. USA, 2003, 100 Suppl 2, 14562-14568.
Gilly, W.F.; Richmond, T.A.; Duda, T.F., Jr.; Elliger, C.; Lebaric,
Z.; Schulz, J.; Bingham, J.P.; Sweedler, J.V. A diverse family of
novel peptide toxins from an unusual cone snail, Conus californi-
cus. J. Exp. Biol., 2010, 214(Pt 1), 147-161.
Craig, A.G.; Bandyopadhyay, P.; Olivera, B.M. Post-translationally
modified neuropeptides from Conus venoms. Eur. J. Biochem.,
1999, 264(2), 271-275.
McIntosh, M.; Cruz, L.J.; Hunkapiller, M.W.; Gray, W.R.; Olivera,
B.M. Isolation and structure of a peptide toxin from the marine
snail Conus magus. Arch. Biochem. Biophys., 1982, 218(1), 329-
Schmidtko, A.; Lotsch, J.; Freynhagen, R.; Geisslinger, G. Zicono-
tide for treatment of severe chronic pain. Lancet, 2010, 375(9725),
Escoubas, P.; Quinton, L.; Nicholson, G.M. Venomics: unravelling
the complexity of animal venoms with mass spectrometry. J. Mass
Spectrom., 2008, 43(3), 279-295.
Prommer, E. Ziconotide: a new option for refractory pain. Drugs
Today (Barc), 2006, 42(6), 369-378.
Bernaldez, J.; Lopez, O.; Licea, A.; Salceda, E.; Arellano, R.O.;
Vega, R.; Soto, E. Electrophysiological characterization of a novel
small peptide from the venom of Conus californicus that targets
voltage-gated neuronal Ca2+ channels. Toxicon, 2010, 57(1), 60-
Calvete, J.J.; Sanz, L.; Angulo, Y.; Lomonte, B.; Gutierrez, J.M.
Venoms, venomics, antivenomics. FEBS Lett., 2009, 583(11),
Gupta, K.; Kumar, M.; Balaram, P. Disulfide bond assignments by
mass spectrometry of native natural peptides: cysteine pairing in
disulfide bonded conotoxins. Anal. Chem., 2010, 82(19), 8313-
Kauferstein, S.; Porth, C.; Kendel, Y.; Wunder, C.; Nicke, A.;
Kordis, D.; Favreau, P.; Koua, D.; Stocklin, R.; Mebs, D. Venomic
study on cone snails (Conus spp.) from South Africa. Toxicon,
2011, 57(1), 28-34.
Vetter, I.; Davis, J.L.; Rash, L.D.; Anangi, R.; Mobli, M.; Ale-
wood, P.F.; Lewis, R.J.; King, G.F. Venomics: a new paradigm for
natural products-based drug discovery. Amino Acids, 2011, 40(1),
Kem, W.R. Anthozoan Neurotoxins. In: Handbook of Neurotoxi-
cology, Massaro, E.J., Ed.; Humana Press: New Jersey, 2002; Vol.
Dutertre, S.; Lewis, R.J. Use of venom peptides to probe ion chan-
nel structure and function. J. Biol. Chem., 2010, 285(18), 13315-
 Beress, L.; Beress, R. Purification of three polypeptides with
neuro- and cardiotoxic activity from the sea anemone Anemonia
sulcata. Toxicon, 1975, 13(5), 359-367.
Norton, T.R.; Shibata, S.; Kashiwagi, M.; Bentley, J. Isolation and
characterization of the cardiotonic polypeptide anthopleurin-A
from the sea anemone Anthopleura xanthogrammica. J. Pharm.
Sci., 1976, 65(9), 1368-1374.
Aneiros, A.; Garcia, I.; Martinez, J.R.; Harvey, A.L.; Anderson,
A.J.; Marshall, D.L.; Engstrom, A.; Hellman, U.; Karlsson, E. A
potassium channel toxin from the secretion of the sea anemone
Bunodosoma granulifera. Isolation, amino acid sequence and bio-
logical activity. Biochim. Biophys. Acta, 1993, 1157(1), 86-92.
Castaneda, O.; Sotolongo, V.; Amor, A.M.; Stocklin, R.; Anderson,
A.J.; Harvey, A.L.; Engstrom, A.; Wernstedt, C.; Karlsson, E.
Characterization of a potassium channel toxin from the Caribbean
Sea anemone Stichodactyla helianthus. Toxicon, 1995, 33(5), 603-
Chagot, B.; Escoubas, P.; Diochot, S.; Bernard, C.; Lazdunski, M.;
Darbon, H. Solution structure of APETx2, a specific peptide inhibi-
tor of ASIC3 proton-gated channels. Protein Sci., 2005, 14(8),
Diochot, S.; Baron, A.; Rash, L.D.; Deval, E.; Escoubas, P.;
Scarzello, S.; Salinas, M.; Lazdunski, M. A new sea anemone pep-
tide, APETx2, inhibits ASIC3, a major acid-sensitive channel in
sensory neurons. EMBO J., 2004, 23(7), 1516-1525.
Diochot, S.; Schweitz, H.; Beress, L.; Lazdunski, M. Sea anemone
peptides with a specific blocking activity against the fast inactivat-
ing potassium channel Kv3.4. J. Biol. Chem., 1998, 273(12), 6744-
Schweitz, H.; Bruhn, T.; Guillemare, E.; Moinier, D.; Lancelin,
J.M.; Beress, L.; Lazdunski, M. Kalicludines and kaliseptine. Two
different classes of sea anemone toxins for voltage sensitive K+
channels. J. Biol. Chem., 1995, 270(42), 25121-25126.
Diochot, S.; Loret, E.; Bruhn, T.; Beress, L.; Lazdunski, M.
APETx1, a new toxin from the sea anemone Anthopleura elegantis-
sima, blocks voltage-gated human ether-a-go-go-related gene po-
tassium channels. Mol. Pharmacol., 2003, 64(1), 59-69.
Sanchez, J.; Bruhn, T.; Aneiros, A.; Wachter, E.; Beress, L. A
simple biochemical method in the search for bioactive polypeptides
in a sea anemone (Anemonia sulcata). Toxicon, 1996, 34(11-12),
Standker, L.; Beress, L.; Garateix, A.; Christ, T.; Ravens, U.; Sal-
ceda, E.; Soto, E.; John, H.; Forssmann, W.G.; Aneiros, A. A new
toxin from the sea anemone Condylactis gigantea with effect on
sodium channel inactivation. Toxicon, 2006, 48(2), 211-220.
Honma, T.; Kawahata, S.; Ishida, M.; Nagai, H.; Nagashima, Y.;
Shiomi, K. Novel peptide toxins from the sea anemone Stichodac-
tyla haddoni. Peptides(NY), 2008, 29(4), 536-544.
Honma, T.; Hasegawa, Y.; Ishida, M.; Nagai, H.; Nagashima, Y.;
Shiomi, K. Isolation and molecular cloning of novel peptide toxins
from the sea anemone Antheopsis maculata. Toxicon, 2005, 45(1),
Nagai, H.; Takuwa, K.; Nakao, M.; Ito, E.; Miyake, M.; Noda, M.;
Nakajima, T. Novel proteinaceous toxins from the box jellyfish
(sea wasp) Carybdea rastoni. Biochem. Biophys. Res. Commun.,
2000, 275(2), 582-588.
Nagai, H.; Takuwa, K.; Nakao, M.; Sakamoto, B.; Crow, G.L.;
Nakajima, T. Isolation and characterization of a novel protein toxin
from the Hawaiian box jellyfish (sea wasp) Carybdea alata. Bio-
chem. Biophys. Res. Commun., 2000, 275(2), 589-594.
Rottini, G.; Gusmani, L.; Parovel, E.; Avian, M.; Patriarca, P. Puri-
fication and properties of a cytolytic toxin in venom of the jellyfish
Carybdea marsupialis. Toxicon, 1995, 33(3), 315-326.
Sanchez-Rodriguez, J.; Torrens, E.; Segura-Puertas, L. Partial
purification and characterization of a novel neurotoxin and three
cytolysins from box jellyfish (Carybdea marsupialis) nematocyst
venom. Arch. Toxicol., 2006, 80(3), 163-168.
Tincu, J.A.; Taylor, S.W. Antimicrobial peptides from marine
invertebrates. Antimicrob. Agents Chemother., 2004, 48(10), 3645-
Rameshkumar, G.; Aravindhan, T.; Ravichandran, S. Antimicrobial
proteins from Charybdis lucifera (Fabricius, 1798). Middle-East J.
Sci. Res., 2009, 4(1), 40-43.
Rameshkumar, G.; Ravichandran, S.; Kaliyavarathan, G.; Ajith-
Kumar, T.T. Antimicrobial peptide from the crab, Thalamita cre-
Bioactive Peptides from Marine Organisms Protein & Peptide Letters, 2012, Vol. 19, No. 7 707 Download full-text
nata (Latreille, 1829). World Journal of Fish and Marine Sciences,
2009, 1(2), 74-79.
Stensvag, K.; Haug, T.; Sperstad, S.V.; Rekdal, O.; Indrevoll, B.;
Styrvold, O.B. Arasin 1, a proline-arginine-rich antimicrobial pep-
tide isolated from the spider crab, Hyas araneus. Dev. Comp. Im-
munol., 2008, 32(3), 275-285.
Auerbach, P.S. Hazardous marine animals. Emerg. Med. Clin.
North. Am., 1984, 2(3), 531-544.
Mebs, D. A toxin from the sea urchin Tripneustes gratilla. Toxicon,
1984, 22(2), 306-307.
Nakagawa, H.; Kimura, A. Partial purification and characterization
of a toxic substance from pedicellariae of the sea urchin
Toxopneustes pileolus. Jpn. J. Pharmacol., 1982, 32(5), 966-968.
Nakagawa, H.; Tu, A.T.; Kimura, A. Purification and characteriza-
tion of Contractin A from the pedicellarial venom of sea urchin,
Toxopneustes pileolus. Arch. Biochem. Biophys., 1991, 284(2),
Li, C.; Haug, T.; Styrvold, O.B.; Jorgensen, T.O.; Stensvag, K.
Strongylocins, novel antimicrobial peptides from the green sea ur-
chin, Strongylocentrotus droebachiensis. Dev. Comp. Immunol.,
2008, 32(12), 1430-1440.
Karasudani, I.; Koyama, T.; Nakandakari, S.; Aniya, Y. Purifica-
tion of anticoagulant factor from the spine venom of the crown-of-
thorns starfish, Acanthaster planci. Toxicon, 1996, 34(8), 871-879.
Shiomi, K.A.; Kazama, A.; Shimakura, K.; Nagashima, Y. Purifi-
cation and properties of phospholipases A2 from the crown-of-
thorns starfish (Acanthaster planci) venom. Toxicon, 1998, 36(4),
Shiomi, K.; Yamamoto, S.; Yamanaka, H.; Kikuchi, T. Purification
and characterization of a lethal factor in venom from the crown-of-
thorns starfish (Acanthaster planci). Toxicon, 1988, 26(11), 1077-
Kem, W.R.; Blumenthal, K.M. Purification and characterization of
the cytotoxic Cerebratulus A toxins. J. Biol. Chem., 1978, 253(16),
Kem, W.R. Purification and characterization of a new family of
polypeptide neurotoxins from the heteronemertine Cerebratulus
lacteus (Leidy). J. Biol. Chem., 1976, 251(14), 4184-4192.
Ovchinnikova, T.V.; Aleshina, G.M.; Balandin, S.V.; Krasnos-
dembskaya, A.D.; Markelov, M.L.; Frolova, E.I.; Leonova, Y.F.;
Tagaev, A.A.; Krasnodembsky, E.G.; Kokryakov, V.N. Purifica-
tion and primary structure of two isoforms of arenicin, a novel an-
timicrobial peptide from marine polychaeta Arenicola marina.
FEBS Lett., 2004, 577(1-2), 209-214.
Jo, H.Y.; Jung, W.K.; Kim, S.K. Purification and characterization
of a novel anticoagulant peptide from marine echiuroid worm, Ure-
chis unicinctus. Process Biochem., 2008, 43, 179-184.
Cole, A.M.; Weis, P.; Diamond, G. Isolation and characterization
of pleurocidin, an antimicrobial peptide in the skin secretions of
winter flounder. J. Biol. Chem., 1997, 272(18), 12008-12013.
 Low, W.K.; Lin, Q.; Stathakis, C.; Miao, M.; Fletcher, G.L.; Hew,
C.L. Isolation and characterization of skin-type, type I antifreeze
polypeptides from the longhorn sculpin, Myoxocephalus octode-
cemspinosus. J. Biol. Chem., 2001, 276(15), 11582-11589.
Evans, R.P.; Fletcher, G.L. Isolation and purification of antifreeze
proteins from skin tissues of snailfish, cunner and sea raven. Bio-
chim. Biophys. Acta, 2004, 1700(2), 209-217.
Iijima, N.; Tanimoto, N.; Emoto, Y.; Morita, Y.; Uematsu, K.;
Murakami, T.; Nakai, T. Purification and characterization of three
isoforms of chrysophsin, a novel antimicrobial peptide in the gills
of the red sea bream, Chrysophrys major. Eur. J. Biochem., 2003,
Lu, Z.; Van Wagoner, R.M.; Harper, M.K.; Baker, H.L.; Hooper,
J.N.; Bewley, C.A.; Ireland, C.M. Mirabamides E-H, HIV-
inhibitory depsipeptides from the sponge Stelletta clavosa. J. Nat.
Prod., 2011, 74(2), 185-193.
Craig, A.G.; Zafaralla, G.; Cruz, L.J.; Santos, A.D.; Hillyard, D.R.;
Dykert, J.; Rivier, J.E.; Gray, W.R.; Imperial, J.; DelaCruz, R.G.;
Sporning, A.; Terlau, H.; West, P.J.; Yoshikami, D.; Olivera, B.M.
An O-glycosylated neuroexcitatory conus peptide. Biochemistry,
1998, 37(46), 16019-16025.
Cruz, L.J.; Gray, W.R.; Olivera, B.M.; Zeikus, R.D.; Kerr, L.;
Yoshikami, D.; Moczydlowski, E. Conus geographus toxins that
discriminate between neuronal and muscle sodium channels. J.
Biol. Chem., 1985, 260(16), 9280-9288.
Pisarewicz, K.; Mora, D.; Pflueger, F.C.; Fields, G.B.; Mari, F.
Polypeptide chains containing D-gamma-hydroxyvaline. J. Am.
Chem. Soc., 2005, 127(17), 6207-6215.
Zafaralla, G.C.; Ramilo, C.; Gray, W.R.; Karlstrom, R.; Olivera,
B.M.; Cruz, L.J. Phylogenetic specificity of cholinergic ligands: al-
pha-conotoxin SI. Biochemistry, 1988, 27(18), 7102-7105.
Rigby, A.C.; Baleja, J.D.; Furie, B.C.; Furie, B. Three-dimensional
structure of a gamma-carboxyglutamic acid-containing conotoxin,
conantokin G, from the marine snail Conus geographus: the metal-
free conformer. Biochemistry, 1997, 36(23), 6906-6914.
Jimenez, E.C.; Olivera, B.M.; Gray, W.R.; Cruz, L.J. Contryphan is
a D-tryptophan-containing Conus peptide. J. Biol. Chem., 1996,
Pi, C.; Liu, J.; Peng, C.; Liu, Y.; Jiang, X.; Zhao, Y.; Tang, S.;
Wang, L.; Dong, M.; Chen, S.; Xu, A. Diversity and evolution of
conotoxins based on gene expression profiling of Conus litteratus.
Genomics, 2006, 88(6), 809-819.
Ueberheide, B.M.; Fenyo, D.; Alewood, P.F.; Chait, B.T. Rapid
sensitive analysis of cysteine rich peptide venom components.
Proc. Natl. Acad. Sci. USA, 2009, 106(17), 6910-6915.
Loughnan, M.; Bond, T.; Atkins, A.; Cuevas, J.; Adams, D.J.;
Broxton, N.M.; Livett, B.G.; Down, J.G.; Jones, A.; Alewood, P.F.;
Lewis, R.J. alpha-conotoxin EpI, a novel sulfated peptide from Co-
nus episcopatus that selectively targets neuronal nicotinic acetyl-
choline receptors. J. Biol. Chem., 1998, 273(25), 15667-15674.
Received: July 29, 2011 Revised: September 6, 2011 Accepted: February 11, 2012