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Special Issue "Marine Peptides and Their Mimetics"

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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (28 February 2015)

Special Issue Editors

Guest Editor
Dr. Peter Duggan

Leader, Peptides and Peptidomimetics Team, CSIRO Materials Science and Engineering, Bayview Avenue, Clayton VIC 3168, Australia
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Interests: use of modified amino acids, peptides and peptidomimetics in chemical biology
Guest Editor
Dr. Kellie L. Tuck

School of Chemistry, Clayton Campus, Monash University, Victoria 3800, Australia
Website | E-Mail
Fax: +61 (0)3 9905 4597
Interests: synthesis of bioactive compounds (peptidomimetics and natural products) with potential therapeutic applications

Special Issue Information

Dear Colleagues,

The number of bioactive peptides isolated from marine organisms continues to grow. These peptides are found in a range of phyla including Mollusca, Crustacea, Porifera, Cnidaria, Nemertina, Echinodermata and Craniata, as well as a number of fish species. Marine peptides have been shown to possess a range of activities of medical relevance including an ability to interact with a variety of human ion channels.  Marine peptides have also been found to possess antimicrobial, antiviral, anticoagulant and antifreeze properties. 

This special issue will present recent results from the isolation, characterisation and biological evaluation of peptides found in marine organisms. Peptides rarely make good therapeutics and the design, synthesis and testing of small-molecule mimetics of bioactive marine peptides with medical relevance is also the subject of much research, and will also be a focus of this special issue.

Peter Duggan
Dr. Kellie L. Tuck
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).

Keywords

  • marine peptides
  • peptidomimetics
  • cystine knots
  • cone snails
  • structure-activity
  • structure determination
  • biological activity
  • ion channel blockers
  • peptide synthesis

Published Papers (26 papers)

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Research

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Open AccessArticle Use of Natural Antimicrobial Peptides and Bacterial Biopolymers for Cultured Pearl Production
Mar. Drugs 2015, 13(6), 3732-3744; doi:10.3390/md13063732
Received: 5 March 2015 / Revised: 20 May 2015 / Accepted: 27 May 2015 / Published: 11 June 2015
Cited by 3 | PDF Full-text (2686 KB) | HTML Full-text | XML Full-text
Abstract
Cultured pearls are the product of grafting and rearing of Pinctada margaritifera pearl oysters in their natural environment. Nucleus rejections and oyster mortality appear to result from bacterial infections or from an inappropriate grafting practice. To reduce the impact of bacterial infections, synthetic
[...] Read more.
Cultured pearls are the product of grafting and rearing of Pinctada margaritifera pearl oysters in their natural environment. Nucleus rejections and oyster mortality appear to result from bacterial infections or from an inappropriate grafting practice. To reduce the impact of bacterial infections, synthetic antibiotics have been applied during the grafting practice. However, the use of such antibiotics presents a number of problems associated with their incomplete biodegradability, limited efficacy in some cases, and an increased risk of selecting for antimicrobial resistant bacteria. We investigated the application of a marine antimicrobial peptide, tachyplesin, which is present in the Japanese horseshoe crab Tachypleus tridentatus, in combination with two marine bacterial exopolymers as alternative treatment agents. In field studies, the combination treatment resulted in a significant reduction in graft failures vs. untreated controls. The combination of tachyplesin (73 mg/L) with two bacterial exopolysaccharides (0.5% w/w) acting as filming agents, reduces graft-associated bacterial contamination. The survival data were similar to that reported for antibiotic treatments. These data suggest that non-antibiotic treatments of pearl oysters may provide an effective means of improving oyster survival following grafting procedures. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle Structural and Functional Characterization of a Novel α-Conotoxin Mr1.7 from Conus marmoreus Targeting Neuronal nAChR α3β2, α9α10 and α6/α3β2β3 Subtypes
Mar. Drugs 2015, 13(6), 3259-3275; doi:10.3390/md13063259
Received: 23 March 2015 / Accepted: 11 May 2015 / Published: 27 May 2015
Cited by 3 | PDF Full-text (2110 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the present study, we synthesized and, structurally and functionally characterized a novel α4/7-conotoxin Mr1.7 (PECCTHPACHVSHPELC-NH2), which was previously identified by cDNA libraries from Conus marmoreus in our lab. The NMR solution structure showed that
[...] Read more.
In the present study, we synthesized and, structurally and functionally characterized a novel α4/7-conotoxin Mr1.7 (PECCTHPACHVSHPELC-NH2), which was previously identified by cDNA libraries from Conus marmoreus in our lab. The NMR solution structure showed that Mr1.7 contained a 310-helix from residues Pro7 to His10 and a type I β-turn from residues Pro14 to Cys17. Electrophysiological results showed that Mr1.7 selectively inhibited the α3β2, α9α10 and α6/α3β2β3 neuronal nicotinic acetylcholine receptors (nAChRs) with an IC50 of 53.1 nM, 185.7 nM and 284.2 nM, respectively, but showed no inhibitory activity on other nAChR subtypes. Further structure-activity studies of Mr1.7 demonstrated that the PE residues at the N-terminal sequence of Mr1.7 were important for modulating its selectivity, and the replacement of Glu2 by Ala resulted in a significant increase in potency and selectivity to the α3β2 nAChR. Furthermore, the substitution of Ser12 with Asn in the loop2 significantly increased the binding of Mr1.7 to α3β2, α3β4, α2β4 and α7 nAChR subtypes. Taken together, this work expanded our knowledge of selectivity and provided a new way to improve the potency and selectivity of inhibitors for nAChR subtypes. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessArticle Enhanced Control of Bladder-Associated Tumors Using Shrimp Anti-Lipopolysaccharide Factor (SALF) Antimicrobial Peptide as a Cancer Vaccine Adjuvant in Mice
Mar. Drugs 2015, 13(5), 3241-3258; doi:10.3390/md13053241
Received: 9 March 2015 / Accepted: 12 May 2015 / Published: 21 May 2015
Cited by 3 | PDF Full-text (2280 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Shrimp anti-lipopolysaccharide factor (SALF) is an antimicrobial peptide with reported anticancer activities, such as suppression of tumor progression. In this study, we prepared a potential cancer vaccine comprised of SALF in conjunction with the cell lysate of inactivated murine bladder carcinoma cells (MBT-2),
[...] Read more.
Shrimp anti-lipopolysaccharide factor (SALF) is an antimicrobial peptide with reported anticancer activities, such as suppression of tumor progression. In this study, we prepared a potential cancer vaccine comprised of SALF in conjunction with the cell lysate of inactivated murine bladder carcinoma cells (MBT-2), and evaluated its efficacy in a mouse tumor model. Our study shows that SALF added to cell culture media inhibits growth progression of MBT-2, and that SALF together with inactivated MBT-2 lysate elevates the level of inflammasome activity, and modulates the levels of IL-1β, MCP-1, IL-6, IL-12, and TNF-α in mouse macrophages. Immunization of 7, 14, and 21 day-old mice with the vaccine prevented growth of MBT-2 cell-mediated tumors. The vaccine was found to enhance expression of T-cell, cytotoxic T cells, and NK cells in the immunized mice groups. Recruitment of macrophages, T-helper cells, and NK cells was enhanced, but levels of VEGF were decreased in immunized mice. This report provides empirical evidence that our SALF as vaccine adjuvant enhances antitumor immunity in mice. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle Antitumor and Antimicrobial Activity of Some Cyclic Tetrapeptides and Tripeptides Derived from Marine Bacteria
Mar. Drugs 2015, 13(5), 3029-3045; doi:10.3390/md13053029
Received: 21 April 2015 / Revised: 22 April 2015 / Accepted: 6 May 2015 / Published: 15 May 2015
Cited by 1 | PDF Full-text (351 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Marine derived cyclo(Gly-l-Ser-l-Pro-l-Glu) was selected as a lead to evaluate antitumor-antibiotic activity. Histidine was chosen to replace the serine residue to form cyclo(Gly-l-His-l-Pro-l-Glu). Cyclic tetrapeptides (CtetPs) were then synthesized using a solution phase method, and subjected to antitumor and antibiotic assays.
[...] Read more.
Marine derived cyclo(Gly-l-Ser-l-Pro-l-Glu) was selected as a lead to evaluate antitumor-antibiotic activity. Histidine was chosen to replace the serine residue to form cyclo(Gly-l-His-l-Pro-l-Glu). Cyclic tetrapeptides (CtetPs) were then synthesized using a solution phase method, and subjected to antitumor and antibiotic assays. The benzyl group protected CtetPs derivatives, showed better activity against antibiotic-resistant Staphylococcus aureus in the range of 60–120 μM. Benzyl group protected CtetPs 3 and 4, exhibited antitumor activity against several cell lines at a concentration of 80–108 μM. However, shortening the size of the ring to the cyclic tripeptide (CtriP) scaffold, cyclo(Gly-l-Ser-l-Pro), cyclo(Ser-l-Pro-l-Glu) and their analogues showed no antibiotic or antitumor activity. This phenomenon can be explained from their backbone structures. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessArticle Functional Diversity of Anti-Lipopolysaccharide Factor Isoforms in Shrimp and Their Characters Related to Antiviral Activity
Mar. Drugs 2015, 13(5), 2602-2616; doi:10.3390/md13052602
Received: 31 March 2015 / Revised: 17 April 2015 / Accepted: 20 April 2015 / Published: 27 April 2015
Cited by 6 | PDF Full-text (945 KB) | HTML Full-text | XML Full-text
Abstract
Anti-lipopolysaccharide factor (ALF) is a small protein with broad-spectrum antimicrobial activity, which has potential application in the disease control. Previously, we isolated seven ALF isoforms from the Chinese shrimp Fenneropenaeus chinensis. In the present study, their distributions in tissues of shrimp were
[...] Read more.
Anti-lipopolysaccharide factor (ALF) is a small protein with broad-spectrum antimicrobial activity, which has potential application in the disease control. Previously, we isolated seven ALF isoforms from the Chinese shrimp Fenneropenaeus chinensis. In the present study, their distributions in tissues of shrimp were analyzed and the data showed that different isoforms had different expression profiles, which suggested that they might have different functions. Then, the functions of different isoforms were studied by analyzing the antibacterial and antiviral activities of the functional domain of ALFs, the LPS-binding domain (LBD), which were synthesized by chemical methods. Different ALFs showed distinct antibacterial and antiviral activities, which were consistent with their diverse tissue distribution patterns. Sequence analysis on the LBD domain of different isoforms revealed that an identical lysine residue site was specifically conserved in peptides with anti-WSSV activity. In order to confirm whether this lysine residue is critical to the antiviral activity of the peptide, new peptides were synthesized by changing residues at this site. Changing the lysine residue at the specific site to other amino acid residue, the antiviral activity of the peptide apparently decreased. While replacing other residue with a lysine residue at this site in LBD peptide without anti-WSSV activity, the peptide will obtain the antiviral activity to WSSV. These results not only showed us a comprehensive understanding on the function of ALFs from F. chinensis, but also provided clues for the development of ALFs as potential therapeutic drugs to WSSV. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle Piscidin is Highly Active against Carbapenem-Resistant Acinetobacter baumannii and NDM-1-Producing Klebsiella pneumonia in a Systemic Septicaemia Infection Mouse Model
Mar. Drugs 2015, 13(4), 2287-2305; doi:10.3390/md13042287
Received: 1 March 2015 / Revised: 30 March 2015 / Accepted: 1 April 2015 / Published: 14 April 2015
Cited by 5 | PDF Full-text (1294 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study was designed to investigate the antimicrobial activity of two synthetic antimicrobial peptides from an aquatic organism, tilapia piscidin 3 (TP3) and tilapia piscidin 4 (TP4), in vitro and in a murine sepsis model, as compared with ampicillin, tigecycline, and imipenem. Mice
[...] Read more.
This study was designed to investigate the antimicrobial activity of two synthetic antimicrobial peptides from an aquatic organism, tilapia piscidin 3 (TP3) and tilapia piscidin 4 (TP4), in vitro and in a murine sepsis model, as compared with ampicillin, tigecycline, and imipenem. Mice were infected with (NDM-1)-producing K. pneumonia and multi-drug resistant Acinetobacter baumannii, and subsequently treated with TP3, TP4, or antibiotics for different periods of time (up to 168 h). Mouse survival and bacterial colony forming units (CFU) in various organs were measured after each treatment. Toxicity was determined based on observation of behavior and measurement of biochemical parameters. TP3 and TP4 exhibited strong activity against K. pneumonia and A. baumannii in vitro. Administration of TP3 (150 μg/mouse) or TP4 (50 μg/mouse) 30 min after infection with K. pneumonia or A. baumannii significantly increased survival in mice. TP4 was more effective than tigecycline at reducing CFU counts in several organs. TP3 and TP4 were shown to be non-toxic, and did not affect mouse behavior. TP3 and TP4 are able at potentiate anti-Acinetobacter baumannii or anti-Klebsiella pneumonia drug activity, reduce bacterial load, and prevent drug resistance, indicating their potential for use in combating multidrug-resistant bacteria. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle Inhibition of N-Type Calcium Channels by Fluorophenoxyanilide Derivatives
Mar. Drugs 2015, 13(4), 2030-2045; doi:10.3390/md13042030
Received: 21 February 2015 / Revised: 18 March 2015 / Accepted: 26 March 2015 / Published: 13 April 2015
Cited by 1 | PDF Full-text (481 KB) | HTML Full-text | XML Full-text
Abstract
A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment
[...] Read more.
A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment of refractory chronic pain. Despite being significantly less complex than the originally designed mimetics, up to a seven-fold improvement in activity was observed. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessArticle Studies toward the Total Synthesis of Itralamide B and Biological Evaluation of Its Structural Analogs
Mar. Drugs 2015, 13(4), 2085-2104; doi:10.3390/md13042085
Received: 8 February 2015 / Revised: 17 March 2015 / Accepted: 30 March 2015 / Published: 13 April 2015
PDF Full-text (961 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Itralamides A and B were isolated from the lipophilic extract of Lyngbya majuscula collected from the eastern Caribbean. Itralamide B (1) showed cytotoxic activity towards human embryonic kidney cells (HEK293, IC50 = 6 μM). Preliminary studies disapproved the proposed stereochemistry
[...] Read more.
Itralamides A and B were isolated from the lipophilic extract of Lyngbya majuscula collected from the eastern Caribbean. Itralamide B (1) showed cytotoxic activity towards human embryonic kidney cells (HEK293, IC50 = 6 μM). Preliminary studies disapproved the proposed stereochemistry of itralamide. In this paper, we will provide a full account of the total synthesis of four stereoisomers of itralamide B and the results derived from biological tests of these structural congeners. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessArticle Two Novel Antioxidant Nonapeptides from Protein Hydrolysate of Skate (Raja porosa) Muscle
Mar. Drugs 2015, 13(4), 1993-2009; doi:10.3390/md13041993
Received: 21 January 2015 / Revised: 25 March 2015 / Accepted: 26 March 2015 / Published: 3 April 2015
Cited by 2 | PDF Full-text (575 KB) | HTML Full-text | XML Full-text
Abstract
In the current study, the preparation conditions of neutrase hydrolysate (SMH) from skate (Raja porosa) muscle protein were optimized using orthogonal L9(3)4 tests, and R values indicated that pH was the most important factor affecting HO· scavenging activity
[...] Read more.
In the current study, the preparation conditions of neutrase hydrolysate (SMH) from skate (Raja porosa) muscle protein were optimized using orthogonal L9(3)4 tests, and R values indicated that pH was the most important factor affecting HO· scavenging activity of SMH. Under the optimum conditions of pH 7.0, enzymolysis temperature 60 °C, enzyme/substrate ratio (E/S) 2%, and enzymolysis time 5 h, EC50 of SMH on HO· was 2.14 ± 0.17 mg/mL. Using ultrafiltration, gel filtration chromatography, and RP-HPLC, two novel antioxidant nonapeptides (SP-A and SP-B) were isolated from SMH and their amino acid sequences were found to be APPTAYAQS (SP-A) and NWDMEKIWD (SP-B) with calculated molecular masses of 904.98 Da and 1236.38 Da, respectively. Both showed strong antioxidant activities. SP-A and SP-B exhibited good scavenging activities on HO· (EC50 0.390 and 0.176 mg/mL), DPPH· (EC50 0.614 and 0.289 mg/mL), and O2· (EC50 0.215 and 0.132 mg/mL) in a dose-dependent manner. SP-B was also effective against lipid peroxidation in the model system. The aromatic (2Trp), acidic (2Asp and Glu), and basic (Lys) amino acid residues within the sequences of SP-B might account for its pronounced antioxidant activity. The results of this study suggested that protein hydrolysate and peptides from skate muscle might be effective as food additives for retarding lipid peroxidation occurring in foodstuffs. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle Lumazine Peptides from the Marine-Derived Fungus Aspergillus terreus
Mar. Drugs 2015, 13(3), 1290-1303; doi:10.3390/md13031290
Received: 1 December 2014 / Revised: 2 March 2015 / Accepted: 2 March 2015 / Published: 12 March 2015
PDF Full-text (547 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Terrelumamides A (1) and B (2), two new lumazine-containing peptides, were isolated from the culture broth of the marine-derived fungus Aspergillus terreus. From the results of combined spectroscopic and chemical analyses, the structures of these compounds were determined
[...] Read more.
Terrelumamides A (1) and B (2), two new lumazine-containing peptides, were isolated from the culture broth of the marine-derived fungus Aspergillus terreus. From the results of combined spectroscopic and chemical analyses, the structures of these compounds were determined to be linear assemblies of 1-methyllumazine-6-carboxylic acid, an amino acid residue and anthranilic acid methyl ester connected by peptide bonds. These new compounds exhibited pharmacological activity by improving insulin sensitivity, which was evaluated in an adipogenesis model using human bone marrow mesenchymal stem cells. In addition, the compounds exhibited fluorescence changes upon binding to DNA, demonstrating their potential applications to DNA sequence recognition. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle Antimicrobial Activity of Peptides Derived from Olive Flounder Lipopolysaccharide Binding Protein/Bactericidal Permeability-Increasing Protein (LBP/BPI)
Mar. Drugs 2014, 12(10), 5240-5257; doi:10.3390/md12105240
Received: 25 July 2014 / Revised: 18 September 2014 / Accepted: 7 October 2014 / Published: 17 October 2014
Cited by 4 | PDF Full-text (705 KB) | HTML Full-text | XML Full-text
Abstract
We describe the antimicrobial function of peptides derived from the C-terminus of the olive flounder LBP BPI precursor protein. The investigated peptides, namely, ofLBP1N, ofLBP2A, ofLBP4N, ofLBP5A, and ofLBP6A, formed α-helical structures, showing significant antimicrobial activity against several Gram-negative bacteria, Gram-positive bacteria,
[...] Read more.
We describe the antimicrobial function of peptides derived from the C-terminus of the olive flounder LBP BPI precursor protein. The investigated peptides, namely, ofLBP1N, ofLBP2A, ofLBP4N, ofLBP5A, and ofLBP6A, formed α-helical structures, showing significant antimicrobial activity against several Gram-negative bacteria, Gram-positive bacteria, and the yeast Candida albicans, but very limited hemolytic activities. The biological activities of these five analogs were evaluated against biomembranes or artificial membranes for the development of candidate therapeutic agents. Gel retardation studies revealed that peptides bound to DNA and inhibited migration on an agarose gel. In addition, we demonstrated that ofLBP6A inhibited polymerase chain reaction. These results suggested that the ofLBP-derived peptide bactericidal mechanism may be related to the interaction with intracellular components such as DNA or polymerase. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessCommunication Insights into the Toxicological Properties of a Low Molecular Weight Fraction from Zoanthus sociatus (Cnidaria)
Mar. Drugs 2013, 11(8), 2873-2881; doi:10.3390/md11082873
Received: 21 May 2013 / Revised: 13 June 2013 / Accepted: 27 June 2013 / Published: 13 August 2013
Cited by 1 | PDF Full-text (483 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The phylum Cnidaria is an ancient group of venomous animals, specialized in the production and delivery of toxins. Many species belonging to the class Anthozoa have been studied and their venoms often contain a group of peptides, less than 10 kDa, that act
[...] Read more.
The phylum Cnidaria is an ancient group of venomous animals, specialized in the production and delivery of toxins. Many species belonging to the class Anthozoa have been studied and their venoms often contain a group of peptides, less than 10 kDa, that act upon ion channels. These peptides and their targets interact with high affinity producing neurotoxic and cardiotoxic effects, and even death, depending on the dose and the administration pathway. Zoanthiniaria is an order of the Subclass Hexacorallia, class Anthozoa, and unlike sea anemone (order Actiniaria), neither its diversity of toxins nor the in vivo effects of the venoms has been exhaustively explored. In this study we assessed some toxicological tests on mice with a low molecular weight fraction obtained by gel filtration in Sephadex G-50 from Zoanthus sociatus crude extract. The gel filtration chromatogram at 280 nm revealed two major peaks, the highest absorbance corresponding to the low molecular weight fraction. The toxicological effects seem to be mostly autonomic and cardiotoxic, causing death in a dose dependent manner with a LD50 of 792 μg/kg. Moreover, at a dose of 600 μg/kg the active fraction accelerated the KCl-induced lethality in mice. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle Total Synthesis of Fellutamide B and Deoxy-Fellutamides B, C, and D
Mar. Drugs 2013, 11(7), 2382-2397; doi:10.3390/md11072382
Received: 17 April 2013 / Revised: 21 May 2013 / Accepted: 27 May 2013 / Published: 8 July 2013
Cited by 6 | PDF Full-text (772 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to
[...] Read more.
The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to (3R)-hydroxy lauric acid was developed utilizing a Brown allylation reaction followed by an oxidative cleavage-oxidation sequence as the key steps. The activity of these natural products, and natural product analogues was also assessed against Mycobacterium tuberculosis in vitro. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle pH-Dependent Solution Structure and Activity of a Reduced Form of the Host-Defense Peptide Myticin C (Myt C) from the Mussel Mytilus galloprovincialis
Mar. Drugs 2013, 11(7), 2328-2346; doi:10.3390/md11072328
Received: 23 April 2013 / Revised: 30 May 2013 / Accepted: 7 June 2013 / Published: 4 July 2013
Cited by 5 | PDF Full-text (1034 KB) | HTML Full-text | XML Full-text
Abstract
Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found
[...] Read more.
Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found in fish cells overexpressing this HDP. However, the potential antimicrobial properties of any synthetic analogue of Myt C has not yet been analysed. Thus, in this work we have synthesised the sequence of the mature peptide of Myt C variant c and analysed the structure activity relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to results previously reported for oxidized isoforms of mussel myticins, red-MytCc was not active against bacteria at physiological pH and showed a moderate antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus. However, its chemotactic properties remained active. Structure/function studies in neutral and acid environments by means of infrared spectroscopy indicated that the structure of red-MytCc is pH dependent, with acid media increasing its alpha-helical content. Furthermore, red-MytCc was able to efficiently aggregate artificial phospholipid membranes at low pH, as well as to inhibit the Escherichia coli growth, suggesting that this activity is attributable to its more structured form in an acidic environment. All together, these results highlight the dynamic and environmentally sensitive behavior of red-Myt C in solution, and provide important insights into Myt C structure/activity relationships and the requirements to exert its antimicrobial/immunomodulatory activities. On the other hand, the pH-dependent direct antimicrobial activity of Myt C suggests that this HDP may be a suitable template for the development of antimicrobial agents that would function selectively in specific pH environments, which are sorely needed in this “antibiotic-resistance era”. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle Conopeptides from Cape Verde Conus crotchii
Mar. Drugs 2013, 11(6), 2203-2215; doi:10.3390/md11062203
Received: 1 April 2013 / Revised: 20 May 2013 / Accepted: 27 May 2013 / Published: 19 June 2013
Cited by 3 | PDF Full-text (705 KB) | HTML Full-text | XML Full-text
Abstract
Marine Cone snails of the genus Conus contain complex peptide toxins in their venom. Living in tropical habitats, they usually use the powerful venom for self-defense and prey capture. Here, we study Conus crotchii venom duct using a peptide mass-matching approach. The C.
[...] Read more.
Marine Cone snails of the genus Conus contain complex peptide toxins in their venom. Living in tropical habitats, they usually use the powerful venom for self-defense and prey capture. Here, we study Conus crotchii venom duct using a peptide mass-matching approach. The C. crotchii was collected on the Cape Verde archipelago in the Boa Vista Island. The venom was analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). About 488 molecular masses between 700 Da and 3000 Da were searched bymatching with known peptide sequences from UniProtKB protein sequence database. Through this method we were able to identify 12 conopeptides. For validation we considered the error between the experimental molecular mass (monoisotopic) and the calculated mass of less than 0.5 Da. All conopeptides detected belong to the A-, O1-, O2-, O3-, T- and D-superfamilies, which can block Ca2+ channels, inhibit K+ channels and act on nicotinic acetylcholine receptors (nAChRs). Only a few of the detected peptides have a 100% UniProtKB database similarity, suggesting that several of them could be newly discovered marine drugs. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessArticle Subtilomycin: A New Lantibiotic from Bacillus subtilis Strain MMA7 Isolated from the Marine Sponge Haliclona simulans
Mar. Drugs 2013, 11(6), 1878-1898; doi:10.3390/md11061878
Received: 25 April 2013 / Revised: 13 May 2013 / Accepted: 15 May 2013 / Published: 3 June 2013
Cited by 22 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bacteriocins are attracting increased attention as an alternative to classic antibiotics in the fight against infectious disease and multidrug resistant pathogens. Bacillus subtilis strain MMA7 isolated from the marine sponge Haliclona simulans displays a broad spectrum antimicrobial activity, which includes Gram-positive and Gram-negative
[...] Read more.
Bacteriocins are attracting increased attention as an alternative to classic antibiotics in the fight against infectious disease and multidrug resistant pathogens. Bacillus subtilis strain MMA7 isolated from the marine sponge Haliclona simulans displays a broad spectrum antimicrobial activity, which includes Gram-positive and Gram-negative pathogens, as well as several pathogenic Candida species. This activity is in part associated with a newly identified lantibiotic, herein named as subtilomycin. The proposed biosynthetic cluster is composed of six genes, including protein-coding genes for LanB-like dehydratase and LanC-like cyclase modification enzymes, characteristic of the class I lantibiotics. The subtilomycin biosynthetic cluster in B. subtilis strain MMA7 is found in place of the sporulation killing factor (skf) operon, reported in many B. subtilis isolates and involved in a bacterial cannibalistic behaviour intended to delay sporulation. The presence of the subtilomycin biosynthetic cluster appears to be widespread amongst B. subtilis strains isolated from different shallow and deep water marine sponges. Subtilomycin possesses several desirable industrial and pharmaceutical physicochemical properties, including activity over a wide pH range, thermal resistance and water solubility. Additionally, the production of the lantibiotic subtilomycin could be a desirable property should B. subtilis strain MMA7 be employed as a probiotic in aquaculture applications. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessArticle Anti-Microbial, Anti-Biofilm Activities and Cell Selectivity of the NRC-16 Peptide Derived from Witch Flounder, Glyptocephalus cynoglossus
Mar. Drugs 2013, 11(6), 1836-1852; doi:10.3390/md11061836
Received: 26 March 2013 / Revised: 25 April 2013 / Accepted: 3 May 2013 / Published: 28 May 2013
Cited by 10 | PDF Full-text (787 KB) | HTML Full-text | XML Full-text
Abstract
Previous studies had identified novel antimicrobial peptides derived from witch flounder. In this work, we extended the search for the activity of peptide that showed antibacterial activity on clinically isolated bacterial cells and bacterial biofilm. Pseudomonas aeruginosa was obtained from otitis media and
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Previous studies had identified novel antimicrobial peptides derived from witch flounder. In this work, we extended the search for the activity of peptide that showed antibacterial activity on clinically isolated bacterial cells and bacterial biofilm. Pseudomonas aeruginosa was obtained from otitis media and cholelithiasis patients, while Staphylococcus aureus was isolated from otitis media patients. We found that synthetic peptide NRC-16 displays antimicrobial activity and is not sensitive to salt during its bactericidal activity. Interestingly, this peptide also led to significant inhibition of biofilm formation at a concentration of 4–16 μM. NRC-16 peptide is able to block biofilm formation at concentrations just above its minimum inhibitory concentration while conventional antibiotics did not inhibit the biofilm formation except ciprofloxacin and piperacillin. It did not cause significant lysis of human RBC, and is not cytotoxic to HaCaT cells and RAW264.7 cells, thereby indicating its selective antimicrobial activity. In addition, the peptide’s binding and permeation activities were assessed by tryptophan fluorescence, calcein leakage and circular dichroism using model mammalian membranes composed of phosphatidylcholine (PC), PC/cholesterol (CH) and PC/sphingomyelin (SM). These experiments confirmed that NRC-16 does not interact with any of the liposomes but the control peptide melittin did. Taken together, we found that NRC-16 has potent antimicrobial and antibiofilm activities with less cytotoxicity, and thus can be considered for treatment of microbial infection in the future. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle ω-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Cav2.2 Ion Channels
Mar. Drugs 2012, 10(10), 2349-2368; doi:10.3390/md10102349
Received: 12 September 2012 / Revised: 10 October 2012 / Accepted: 12 October 2012 / Published: 22 October 2012
Cited by 12 | PDF Full-text (866 KB) | HTML Full-text | XML Full-text
Abstract
The neuronal voltage-gated N-type calcium channel (Cav2.2) is a validated target for the treatment of neuropathic pain. A small library of anthranilamide-derived ω-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade.
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The neuronal voltage-gated N-type calcium channel (Cav2.2) is a validated target for the treatment of neuropathic pain. A small library of anthranilamide-derived ω-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. These consisted of a 125I-ω-conotoxin GVIA displacement assay, a fluorescence-based calcium response assay with SH-SY5Y neuroblastoma cells, and a whole-cell patch clamp electrophysiology assay with HEK293 cells stably expressing human Cav2.2 channels. A subset of compounds were active in all three assays. This is the first time that compounds designed to be mimics of ω-conotoxin GVIA and found to be active in the 125I-ω-conotoxin GVIA displacement assay have also been shown to block functional ion channels in a dose-dependent manner. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Review

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Open AccessReview Marine Peptides: Bioactivities and Applications
Mar. Drugs 2015, 13(7), 4006-4043; doi:10.3390/md13074006
Received: 30 April 2015 / Revised: 15 June 2015 / Accepted: 18 June 2015 / Published: 29 June 2015
Cited by 8 | PDF Full-text (490 KB) | HTML Full-text | XML Full-text
Abstract
Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic
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Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessReview Emerging Concepts Promising New Horizons for Marine Biodiscovery and Synthetic Biology
Mar. Drugs 2015, 13(5), 2924-2954; doi:10.3390/md13052924
Received: 18 March 2015 / Revised: 22 April 2015 / Accepted: 28 April 2015 / Published: 13 May 2015
Cited by 9 | PDF Full-text (1331 KB) | HTML Full-text | XML Full-text
Abstract
The vast oceans of the world, which comprise a huge variety of unique ecosystems, are emerging as a rich and relatively untapped source of novel bioactive compounds with invaluable biotechnological and pharmaceutical potential. Evidence accumulated over the last decade has revealed that the
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The vast oceans of the world, which comprise a huge variety of unique ecosystems, are emerging as a rich and relatively untapped source of novel bioactive compounds with invaluable biotechnological and pharmaceutical potential. Evidence accumulated over the last decade has revealed that the diversity of marine microorganisms is enormous with many thousands of bacterial species detected that were previously unknown. Associated with this diversity is the production of diverse repertoires of bioactive compounds ranging from peptides and enzymes to more complex secondary metabolites that have significant bioactivity and thus the potential to be exploited for innovative biotechnology. Here we review the discovery and functional potential of marine bioactive peptides such as lantibiotics, nanoantibiotics and peptidomimetics, which have received particular attention in recent years in light of their broad spectrum of bioactivity. The significance of marine peptides in cell-to-cell communication and how this may be exploited in the discovery of novel bioactivity is also explored. Finally, with the recent advances in bioinformatics and synthetic biology, it is becoming clear that the integration of these disciplines with genetic and biochemical characterization of the novel marine peptides, offers the most potential in the development of the next generation of societal solutions. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessReview Conotoxin Gene Superfamilies
Mar. Drugs 2014, 12(12), 6058-6101; doi:10.3390/md12126058
Received: 28 October 2014 / Revised: 29 November 2014 / Accepted: 4 December 2014 / Published: 17 December 2014
Cited by 20 | PDF Full-text (2366 KB) | HTML Full-text | XML Full-text
Abstract
Conotoxins are the peptidic components of the venoms of marine cone snails (genus Conus). They are remarkably diverse in terms of structure and function. Unique potency and selectivity profiles for a range of neuronal targets have made several conotoxins valuable as research
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Conotoxins are the peptidic components of the venoms of marine cone snails (genus Conus). They are remarkably diverse in terms of structure and function. Unique potency and selectivity profiles for a range of neuronal targets have made several conotoxins valuable as research tools, drug leads and even therapeutics, and has resulted in a concerted and increasing drive to identify and characterise new conotoxins. Conotoxins are translated from mRNA as peptide precursors, and cDNA sequencing is now the primary method for identification of new conotoxin sequences. As a result, gene superfamily, a classification based on precursor signal peptide identity, has become the most convenient method of conotoxin classification. Here we review each of the described conotoxin gene superfamilies, with a focus on the structural and functional diversity present in each. This review is intended to serve as a practical guide to conotoxin superfamilies and to facilitate interpretation of the increasing number of conotoxin precursor sequences being identified by targeted-cDNA sequencing and more recently high-throughput transcriptome sequencing. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessReview Antimicrobial Peptides from Marine Proteobacteria
Mar. Drugs 2013, 11(10), 3632-3660; doi:10.3390/md11103632
Received: 12 July 2013 / Revised: 30 July 2013 / Accepted: 5 August 2013 / Published: 30 September 2013
Cited by 18 | PDF Full-text (1224 KB) | HTML Full-text | XML Full-text
Abstract
After years of inadequate use and the emergence of multidrug resistant (MDR) strains, the efficiency of “classical” antibiotics has decreased significantly. New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as a source of unusual bioactive metabolites. However, the
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After years of inadequate use and the emergence of multidrug resistant (MDR) strains, the efficiency of “classical” antibiotics has decreased significantly. New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as a source of unusual bioactive metabolites. However, the potential of marine bacteria, except for Actinomycetes and Cyanobacteria, has been largely underexplored. In the past two decades, the structures of several antimicrobial compounds have been elucidated in marine Proteobacteria. Of these compounds, polyketides (PKs), synthesised by condensation of malonyl-coenzyme A and/or acetyl-coenzyme A, and non-ribosomal peptides (NRPs), obtained through the linkage of (unusual) amino acids, have recently generated particular interest. NRPs are good examples of naturally modified peptides. Here, we review and compile the data on the antimicrobial peptides isolated from marine Proteobacteria, especially NRPs. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessReview Strategies for the Development of Conotoxins as New Therapeutic Leads
Mar. Drugs 2013, 11(7), 2293-2313; doi:10.3390/md11072293
Received: 14 April 2013 / Revised: 27 May 2013 / Accepted: 6 June 2013 / Published: 28 June 2013
Cited by 12 | PDF Full-text (659 KB) | HTML Full-text | XML Full-text
Abstract
Peptide toxins typically bind to their target ion channels or receptors with high potency and selectivity, making them attractive leads for therapeutic development. In some cases the native peptide as it is found in the venom from which it originates can be used
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Peptide toxins typically bind to their target ion channels or receptors with high potency and selectivity, making them attractive leads for therapeutic development. In some cases the native peptide as it is found in the venom from which it originates can be used directly, but in many instances it is desirable to truncate and/or stabilize the peptide to improve its therapeutic properties. A complementary strategy is to display the key residues that make up the pharmacophore of the peptide toxin on a non-peptidic scaffold, thereby creating a peptidomimetic. This review exemplifies these approaches with peptide toxins from marine organisms, with a particular focus on conotoxins. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessReview Protease Inhibitors from Marine Venomous Animals and Their Counterparts in Terrestrial Venomous Animals
Mar. Drugs 2013, 11(6), 2069-2112; doi:10.3390/md11062069
Received: 19 April 2013 / Revised: 28 May 2013 / Accepted: 30 May 2013 / Published: 14 June 2013
Cited by 15 | PDF Full-text (1798 KB) | HTML Full-text | XML Full-text
Abstract
The Kunitz-type protease inhibitors are the best-characterized family of serine protease inhibitors, probably due to their abundance in several organisms. These inhibitors consist of a chain of ~60 amino acid residues stabilized by three disulfide bridges, and was first observed in the bovine
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The Kunitz-type protease inhibitors are the best-characterized family of serine protease inhibitors, probably due to their abundance in several organisms. These inhibitors consist of a chain of ~60 amino acid residues stabilized by three disulfide bridges, and was first observed in the bovine pancreatic trypsin inhibitor (BPTI)-like protease inhibitors, which strongly inhibit trypsin and chymotrypsin. In this review we present the protease inhibitors (PIs) described to date from marine venomous animals, such as from sea anemone extracts and Conus venom, as well as their counterparts in terrestrial venomous animals, such as snakes, scorpions, spiders, Anurans, and Hymenopterans. More emphasis was given to the Kunitz-type inhibitors, once they are found in all these organisms. Their biological sources, specificity against different proteases, and other molecular blanks (being also K+ channel blockers) are presented, followed by their molecular diversity. Whereas sea anemone, snakes and other venomous animals present mainly Kunitz-type inhibitors, PIs from Anurans present the major variety in structure length and number of Cys residues, with at least six distinguishable classes. A representative alignment of PIs from these venomous animals shows that, despite eventual differences in Cys assignment, the key-residues for the protease inhibitory activity in all of them occupy similar positions in primary sequence. The key-residues for the K+ channel blocking activity was also compared. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessReview Antifreeze Peptides and Glycopeptides, and Their Derivatives: Potential Uses in Biotechnology
Mar. Drugs 2013, 11(6), 2013-2041; doi:10.3390/md11062013
Received: 1 April 2013 / Revised: 22 April 2013 / Accepted: 10 May 2013 / Published: 10 June 2013
Cited by 9 | PDF Full-text (1920 KB) | HTML Full-text | XML Full-text
Abstract
Antifreeze proteins (AFPs) and glycoproteins (AFGPs), collectively called AF(G)Ps, constitute a diverse class of proteins found in various Arctic and Antarctic fish, as well as in amphibians, plants, and insects. These compounds possess the ability to inhibit the formation of ice and are
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Antifreeze proteins (AFPs) and glycoproteins (AFGPs), collectively called AF(G)Ps, constitute a diverse class of proteins found in various Arctic and Antarctic fish, as well as in amphibians, plants, and insects. These compounds possess the ability to inhibit the formation of ice and are therefore essential to the survival of many marine teleost fishes that routinely encounter sub-zero temperatures. Owing to this property, AF(G)Ps have potential applications in many areas such as storage of cells or tissues at low temperature, ice slurries for refrigeration systems, and food storage. In contrast to AFGPs, which are composed of repeated tripeptide units (Ala-Ala-Thr)n with minor sequence variations, AFPs possess very different primary, secondary, and tertiary structures. The isolation and purification of AFGPs is laborious, costly, and often results in mixtures, making characterization difficult. Recent structural investigations into the mechanism by which linear and cyclic AFGPs inhibit ice crystallization have led to significant progress toward the synthesis and assessment of several synthetic mimics of AFGPs. This review article will summarize synthetic AFGP mimics as well as current challenges in designing compounds capable of mimicking AFGPs. It will also cover our recent efforts in exploring whether peptoid mimics can serve as structural and functional mimics of native AFGPs. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessReview “Head-to-Side-Chain” Cyclodepsipeptides of Marine Origin
Mar. Drugs 2013, 11(5), 1693-1717; doi:10.3390/md11051693
Received: 12 March 2013 / Revised: 7 April 2013 / Accepted: 23 April 2013 / Published: 21 May 2013
Cited by 18 | PDF Full-text (1514 KB) | HTML Full-text | XML Full-text
Abstract
Since the late 1980s, a large number of depsipeptides that contain a new topography, referred to as “head-to-side-chain” cyclodepsipeptides, have been isolated and characterized. These peptides present a unique structural arrangement that comprises a macrocyclic region closed through an ester bond between the
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Since the late 1980s, a large number of depsipeptides that contain a new topography, referred to as “head-to-side-chain” cyclodepsipeptides, have been isolated and characterized. These peptides present a unique structural arrangement that comprises a macrocyclic region closed through an ester bond between the C-terminus and a β-hydroxyl group, and terminated with a polyketide moiety or a more simple branched aliphatic acid. This structural pattern, the presence of unique and complex residues, and relevant bioactivity are the main features shared by all the members of this new class of depsipeptides, which are reviewed herein. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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