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Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential - III

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

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 15184

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Prof. Dr. Tatiana V. Ovchinnikova

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Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
Interests: marine natural products; marine peptides; innate immunity; host defense peptides; molecular mechanisms of antimicrobial and anticancer activity; structure elucidation; structure-function relationship; bioengineering; drug design; peptide antibiotics; peptide anticancer agents; drug resistance; bioorganic chemistry; biotechnology
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Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of a previous successful Special Issue series (Version I: Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential; Version II: Marine Bioactive Peptides II: Structure, Function, and Therapeutic Potential).
https://www.mdpi.com/journal/marinedrugs/special_issues/Marine_Bioactive_Peptides
https://www.mdpi.com/journal/marinedrugs/special_issues/Marine_Bioactive_Peptides_II

Marine peptides that are diverse in structure and function have been found in various phyla, and their number has dynamically grown in recent years. Some of them are evolutionary ancient molecular factors of innate immunity that play a key role in host defense. A plethora of biological activities, including antibacterial, antifungal, antiviral, cytotoxic, neurotoxic, anticoagulant, antifreeze, endotoxin-binding, and immune-modulating, make marine peptides an attractive molecular basis for the design of innovative antibiotics, anticancer drugs, analgesics, medicines for neurological disorders, etc.

The third edition of the Special Issue “Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential” aims to collect papers on up-to-date information regarding the isolation, structural elucidation, functional characterization, and therapeutic potential evaluation of peptides isolated from marine organisms. The chemical synthesis and biotechnological production of marine peptides and their mimetics will also be a focus of this Special Issue. In addition, this Special Issue will publish new results arising from peptidomic approaches.

Prof. Dr. Tatiana V. Ovchinnikova
Guest Editor

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind 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 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

marine peptides
structure
function
chemical synthesis
biotechnological production
peptidomics
therapeutic potential
antibacterial
antifungal
antiviral
cytotoxic
neurotoxic
anticancer
anticoagulant
endotoxin-binding
host defense
innate immunity
toxins
peptide drugs

Related Special Issues

Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential IV in Marine Drugs (6 articles)
Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential in Marine Drugs (25 articles)
Marine Bioactive Peptides II: Structure, Function, and Therapeutic Potential in Marine Drugs (11 articles)

Published Papers (8 papers)

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Research

Jump to: Review

51 pages, 7612 KiB

Open AccessArticle

Polypharmacological Cell-Penetrating Peptides from Venomous Marine Animals Based on Immunomodulating, Antimicrobial, and Anticancer Properties

by Shiva Hemmati and Haniyeh Rasekhi Kazerooni

Mar. Drugs 2022, 20(12), 763; https://doi.org/10.3390/md20120763 - 04 Dec 2022

Cited by 5 | Viewed by 2632

Abstract

Complex pathological diseases, such as cancer, infection, and Alzheimer’s, need to be targeted by multipronged curative. Various omics technologies, with a high rate of data generation, demand artificial intelligence to translate these data into druggable targets. In this study, 82 marine venomous animal species were retrieved, and 3505 cryptic cell-penetrating peptides (CPPs) were identified in their toxins. A total of 279 safe peptides were further analyzed for antimicrobial, anticancer, and immunomodulatory characteristics. Protease-resistant CPPs with endosomal-escape ability in Hydrophis hardwickii, nuclear-localizing peptides in Scorpaena plumieri, and mitochondrial-targeting peptides from Synanceia horrida were suitable for compartmental drug delivery. A broad-spectrum S. horrida-derived antimicrobial peptide with a high binding-affinity to bacterial membranes was an antigen-presenting cell (APC) stimulator that primes cytokine release and naïve T-cell maturation simultaneously. While antibiofilm and wound-healing peptides were detected in Synanceia verrucosa, APC epitopes as universal adjuvants for antiviral vaccination were in Pterois volitans and Conus monile. Conus pennaceus-derived anticancer peptides showed antiangiogenic and IL-2-inducing properties with moderate BBB-permeation and were defined to be a tumor-homing peptide (THP) with the ability to inhibit programmed death ligand-1 (PDL-1). Isoforms of RGD-containing peptides with innate antiangiogenic characteristics were in Conus tessulatus for tumor targeting. Inhibitors of neuropilin-1 in C. pennaceus are proposed for imaging probes or therapeutic delivery. A Conus betulinus cryptic peptide, with BBB-permeation, mitochondrial-targeting, and antioxidant capacity, was a stimulator of anti-inflammatory cytokines and non-inducer of proinflammation proposed for Alzheimer’s. Conclusively, we have considered the dynamic interaction of cells, their microenvironment, and proportional-orchestrating-host- immune pathways by multi-target-directed CPPs resembling single-molecule polypharmacology. This strategy might fill the therapeutic gap in complex resistant disorders and increase the candidates’ clinical-translation chance. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential - III)

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17 pages, 3531 KiB

Open AccessArticle

The Antimicrobial Peptide LJ-hep2 from Lateolabrax japonicus Exerting Activities against Multiple Pathogenic Bacteria and Immune Protection In Vivo

by Ruihao Gong, Zhe An, Weibin Zhang, Fangyi Chen and Ke-Jian Wang

Mar. Drugs 2022, 20(10), 651; https://doi.org/10.3390/md20100651 - 20 Oct 2022

Cited by 4 | Viewed by 1965

Abstract

Hepcidin is widely present in many kinds of fish and is an important innate immune factor. A variety of HAMP2-type hepcidins have strong antimicrobial activity and immunomodulatory functions and are expected to be developed as substitutes for antibiotics. In this study, the antimicrobial activity of Hepc2 from Japanese seabass (Lateolabrax japonicus) (designated as LJ-hep2) was investigated using its recombinant precursor protein (rLJ-hep2) expressed in Pichia pastoris and a chemically synthesized mature peptide (LJ-hep2_(66–86)). The results showed that both rLJ-hep2 and synthetic LJ-hep2_(66–86) displayed broad antimicrobial spectrum with potent activity against gram-negative and gram-positive bacteria, and fungi. Especially, LJ-hep2_(66–86) had stronger antimicrobial activity and exhibited potent activity against several clinically isolated multidrug-resistant bacteria, including Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterococcus faecium. Moreover, LJ-hep2_(66–86) exerted rapid bactericidal kinetic (killed tested bacteria within 2 h), induced significant morphological changes and promoted agglutination of E. coli, P. aeruginosa and Aeromonas hydrophila. The activity of LJ-hep2_(66–86) against E. coli, P. aeruginosa and A. hydrophila was stable and remained active when heated for 30 min. In addition, LJ-hep2_(66–86) exhibited no cytotoxicity to the mammalian cell line HEK293T and fish cell lines (EPC and ZF4). In vivo study showed that LJ-hep2_(66–86) could improve the survival rate of marine medaka (Oryzias melastigma) by about 40% under the challenge of A. hydrophila, indicating its immunoprotective function. Taken together, both rLJ-hep2 and LJ-hep2_(66–86) have good prospects to be used as potential antimicrobial agents in aquaculture and medicine in the future. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential - III)

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10 pages, 1009 KiB

Open AccessArticle

In Vitro Modulation of Complement Activation by Therapeutically Prospective Analogues of the Marine Polychaeta Arenicin Peptides

by Ilia A. Krenev, Pavel V. Panteleev, Ekaterina S. Umnyakova, Nikolay P. Gorbunov, Valeria A. Kostevich, Sergey V. Balandin, Tatiana V. Ovchinnikova, Galina M. Aleshina and Mikhail N. Berlov

Mar. Drugs 2022, 20(10), 612; https://doi.org/10.3390/md20100612 - 28 Sep 2022

Cited by 3 | Viewed by 1363

Abstract

The widespread resistance to antibiotics in pathogenic bacteria makes the development of a new generation of antimicrobials an urgent task. The development of new antibiotics must be accompanied by a comprehensive study of all of their biological activities in order to avoid adverse side-effects from their application. Some promising antibiotic prototypes derived from the structures of arenicins, antimicrobial peptides from the lugworm Arenicola marina, have been developed. Previously, we described the ability of natural arenicins -1 and -2 to modulate the human complement system activation in vitro. In this regard, it seems important to evaluate the effect of therapeutically promising arenicin analogues on complement activation. Here, we describe the complement-modulating activity of three such analogues, Ar-1[V8R], ALP1, and AA139. We found that the mode of action of Ar-1[V8R] and ALP1 on the complement was similar to that of natural arenicins, which can both activate and inhibit the complement, depending on the concentration. However, Ar-1[V8R] behaved predominantly as an inhibitor, showing only a moderate increase in C3a production in the alternative pathway model and no enhancement at all of the classical pathway of complement activation. In contrast, the action of ALP1 was characterized by a marked increase in the complement activation through the classical pathway in the concentration range of 2.5–20 μg/mL. At the same time, at higher concentrations (80–160 μg/mL), this peptide exhibited a complement inhibitory effect characteristic of the other arenicins. Peptide AA139, like other arenicins, exhibited an inhibitory effect on complement at a concentration of 160 μg/mL, but was much less pronounced. Overall, our results suggest that the effect on the complement system should be taken into account in the development of antibiotics based on arenicins. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential - III)

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18 pages, 3355 KiB

Open AccessArticle

Antibacterial and Anticancer Activities of Pleurocidin-Amide, a Potent Marine Antimicrobial Peptide Derived from Winter Flounder, Pleuronectes americanus

by Hui-Chen Hsu, Ming-Hsin Chen, Ming-Lung Yeh and Wei-Jung Chen

Mar. Drugs 2022, 20(8), 519; https://doi.org/10.3390/md20080519 - 14 Aug 2022

Cited by 6 | Viewed by 2022

Abstract

The extensive use of conventional antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. Evidence suggests that cationic antimicrobial peptides (AMPs) have the greatest potential to serve as traditional antibiotic substitutes. Recent studies have also reported that certain AMPs have selective toxicity toward various types of cancer cells. The electrostatic attraction between the negatively charged membrane components and AMPs is believed to play a crucial role in the disruption of bacterial and cancer cell membranes. In the current study, we used a potent AMP called Pleurocidin (Ple) derived from winter flounder Pleuronectes americanus and its C-terminal-amidated derivative Pleurocidin-amide (Ple-a), and evaluated their antibacterial and anticancer activities. Our results indicated that both Ple and Ple-a exhibited significant antibacterial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, especially marine pathogens, with MIC values ranging from 0.25 to 32 μg/mL. These peptides are also potent against several multidrug-resistant (MDR) bacterial strains, with MIC values ranging from 2 to 256 μg/mL. When used in combination with certain antibiotics, they exhibited a synergistic effect against MDR E. coli. Ple and Ple-a also showed notable cytotoxicity toward various cancer cell lines, with IC₅₀ values ranging from 11 to 340 μM, while normal mouse fibroblast 3T3 cells were less susceptible to these peptides. Ple-a was then selected to study its anticancer mechanism toward A549 human lung adenocarcinoma cells. Western blot analysis and confocal microscopy showed that Ple-a could inhibit autophagy of A549 cells, and induce apoptosis 48 h after treatment. Our findings provided support for the future application of Ple-a as potential therapeutic agent for bacterial infections and cancer treatment. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential - III)

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19 pages, 2429 KiB

Open AccessArticle

Novel β-Hairpin Peptide from Marine Polychaeta with a High Efficacy against Gram-Negative Pathogens

by Victoria N. Safronova, Ilia A. Bolosov, Roman N. Kruglikov, Olga V. Korobova, Eugenia S. Pereskokova, Alexander I. Borzilov, Pavel V. Panteleev and Tatiana V. Ovchinnikova

Mar. Drugs 2022, 20(8), 517; https://doi.org/10.3390/md20080517 - 13 Aug 2022

Cited by 6 | Viewed by 1908

Abstract

In recent years, new antibiotics targeting multidrug resistant Gram-negative bacteria have become urgently needed. Therefore, antimicrobial peptides are considered to be a novel perspective class of antibacterial agents. In this study, a panel of novel BRICHOS-related β-hairpin antimicrobial peptides were identified in transcriptomes of marine polychaeta species. Two of them—abarenicin from Abarenicola pacifica and UuBRI-21 from Urechis unicinctus—possess strong antibacterial potential in vitro against a wide panel of Gram-negative bacteria including drug-resistant strains. Mechanism of action assays demonstrate that peptides disrupt bacterial and mammalian membrane integrity. Considering the stronger antibacterial potential and a low ability of abarenicin to be bound by components of serum, this peptide was selected for further modification. We conducted an alanine and arginine scanning of abarenicin by replacing individual amino acids and modulating hydrophobicity so as to improve its antibacterial potency and membrane selectivity. This design approach allowed us to obtain the Ap9 analog displaying a high efficacy in vivo in the mice septicemia and neutropenic mice peritonitis models. We demonstrated that abarenicin analogs did not significantly induce bacterial resistance after a four-week selection experiment and acted on different steps of the biofilm formation: (a) killing bacteria at their planktonic stage and preventing biofilm formation and (b) degrading pre-formed biofilm and killing embedded bacteria. The potent antibacterial and antibiofilm activity of the abarenicin analog Ap9 with its high efficacy in vivo against Gram-negative infection in mice models makes this peptide an attractive candidate for further preclinical investigation. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential - III)

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14 pages, 1488 KiB

Open AccessArticle

The Effects of Freshwater Clam (Corbicula fluminea) Extract on Serum Tumor Necrosis Factor-Alpha (TNF-α) in Prediabetic Patients in Taiwan

by Tse-Hung Huang, Chiao-Hsu Ke, Chin-Chang Chen, Cheng-Hsun Chuang, Kuang-Wen Liao, Yi-Hsien Shiao and Chen-Si Lin

Mar. Drugs 2022, 20(4), 261; https://doi.org/10.3390/md20040261 - 10 Apr 2022

Cited by 3 | Viewed by 2840

Abstract

Freshwater clam extract (FCE) is a functional food that regulates the immune system and has been demonstrated in numerous studies to display desirable anti–tumor necrosis factor-alpha (TNF-α) responses. In addition, excess TNF-α production is positively associated with type 2 diabetes. However, few longitudinal clinical studies evaluating the efficiency and toxicity of FCE are available. This article reports that patients with prediabetes who received FCE had a desirable outcome of a reduction in serum TNF-α for a long period. This was a double-blind, randomized, parallel clinical trial conducted using FCE intervention and placebo groups, and 36 patients with prediabetes were enrolled. Two grams of FCE or placebo was consumed daily for 180 consecutive days. The serum of the participants was collected at four time points (0M: before the intervention; 3M: after 3 months of intervention; 6M: after 6 months of intervention; 12M: 6 months after cessation of intervention at 6M). A serum TNF-α concentration higher than 4.05 pg/mL was defined as a cut-off value. FCE reduced serum TNF-α in all participants at 6M and 12M. Moreover, FCE significantly suppressed serum TNF-α concentrations at 6M and 12M and inhibited TNF-α release with time series in subjects with elevated TNF-α values. FCE intervention effectively reduced serum TNF-α and persistently sustained the effects for half a year in patients with prediabetes. Gas chromatography–mass spectrometry (GS-MS) analysis revealed that the major components of FCE were phytosterols and fatty acids, which exerted anti-inflammatory and anti-TNF-α abilities. Hence, FCE has the potential to be developed as a natural treatment for prediabetic patients in Taiwan. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential - III)

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15 pages, 2513 KiB

Open AccessArticle

Mechanism of Action and Therapeutic Potential of the β-Hairpin Antimicrobial Peptide Capitellacin from the Marine Polychaeta Capitella teleta

by Victoria N. Safronova, Pavel V. Panteleev, Stanislav V. Sukhanov, Ilia Y. Toropygin, Ilia A. Bolosov and Tatiana V. Ovchinnikova

Mar. Drugs 2022, 20(3), 167; https://doi.org/10.3390/md20030167 - 25 Feb 2022

Cited by 20 | Viewed by 3008

Abstract

Among the most potent and proteolytically resistant antimicrobial peptides (AMPs) of animal origin are molecules forming a β-hairpin structure stabilized by disulfide bonds. In this study, we investigated the mechanism of action and therapeutic potential of the β-hairpin AMP from the marine polychaeta Capitella teleta, named capitellacin. The peptide exhibits a low cytotoxicity toward mammalian cells and a pronounced activity against a wide range of bacterial pathogens including multi-resistant bacteria, but the mechanism of its antibacterial action is still obscure. In view of this, we obtained analogs of capitellacin and tachyplesin-inspired chimeric variants to identify amino acid residues important for biological activities. A low hydrophobicity of the β-turn region in capitellacin determines its modest membranotropic activity and slow membrane permeabilization. Electrochemical measurements in planar lipid bilayers mimicking the E. coli membrane were consistent with the detergent-like mechanism of action rather than with binding to a specific molecular target in the cell. The peptide did not induce bacterial resistance after a 21-day selection experiment, which also pointed at a membranotropic mechanism of action. We also found that capitellacin can both prevent E. coli biofilm formation and destroy preformed mature biofilms. The marked antibacterial and antibiofilm activity of capitellacin along with its moderate adverse effects on mammalian cells make this peptide a promising scaffold for the development of drugs for the treatment of chronic E. coli infections, in particular those caused by the formation of biofilms. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential - III)

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Review

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18 pages, 1163 KiB

Open AccessReview

Innate Immunity Mechanisms in Marine Multicellular Organisms

by Svetlana V. Guryanova and Tatiana V. Ovchinnikova

Mar. Drugs 2022, 20(9), 549; https://doi.org/10.3390/md20090549 - 25 Aug 2022

Cited by 7 | Viewed by 2425

Abstract

The innate immune system provides an adequate response to stress factors and pathogens through pattern recognition receptors (PRRs), located on the surface of cell membranes and in the cytoplasm. Generally, the structures of PRRs are formed by several domains that are evolutionarily conserved, with a fairly high degree of homology in representatives of different species. The orthologs of TLRs, NLRs, RLRs and CLRs are widely represented, not only in marine chordates, but also in invertebrates. Study of the interactions of the most ancient marine multicellular organisms with microorganisms gives us an idea of the evolution of molecular mechanisms of protection against pathogens and reveals new functions of already known proteins in ensuring the body’s homeostasis. The review discusses innate immunity mechanisms of protection of marine invertebrate organisms against infections, using the examples of ancient multicellular hydroids, tunicates, echinoderms, and marine worms in the context of searching for analogies with vertebrate innate immunity. Due to the fact that mucous membranes first arose in marine invertebrates that have existed for several hundred million years, study of their innate immune system is both of fundamental importance in terms of understanding molecular mechanisms of host defense, and of practical application, including the search of new antimicrobial agents for subsequent use in medicine, veterinary and biotechnology. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential - III)

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