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Design and Synthesis of Biologically Active Peptides

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 5543

Special Issue Editor


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Guest Editor
Technological University Dublin, Dublin, Ireland
Interests: chemical peptide synthesis; solid-phase peptide synthesis; antimicrobial peptides; lanthipeptides; lantibiotics; unusual amino acids; peptidomimetics; antimicrobial resistance; greener chemical peptide synthesis

Special Issue Information

Naturally occurring biologically active peptides, and their derivatives, continue to be a source of potential therapeutics, with the number of such compounds being developed continuing to rise. Using these as a starting point or template, the number of research groups and companies involved in the design and synthesis of biologically active peptides, and their many derivatives, is also growing significantly. By their nature, peptides reside on the spectrum between the small molecules and the larger proteins/biologics. Peptides are usually amenable to chemical synthesis like small molecules, as well as retaining the exquisite selectivity of larger proteins. The introduction of solid-phase peptide synthesis by Bruce Merrifield in the 1960s revolutionized the chemical synthesis of peptides, which, along with newer ligation technologies, has meant that the synthesis of complex peptides has now become more “routine”, on par with small molecules.

In parallel, significant advances in spectroscopic, spectrometric, and computational capability, from both a hardware and software perspective, has allowed the de novo design of novel peptide entities, with a range of built-in, specifically targeted properties, to become mainstream. The study of peptide–protein interactions, both computationally and spectroscopically, has also progressed at a rapid pace, where new therapies, and other applications, will be developed in the coming years.

The main aim of this Special Issue is to highlight the wealth of research taking place throughout the world in the “peptide design and synthesis” arena. Contributions to this issue, in the form of original research papers, or review articles, in the area of the design of novel peptides, to computational studies, to their chemical synthesis or semi-synthesis, along with the associated methodology development, will be very welcome.

Dr. Fintan Kelleher
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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

  • de novo design of biologically active peptides and derivatives
  • SPPS of biologically active peptides and derivatives
  • antimicrobial peptide design and synthesis
  • anticancer peptides and metallopeptides
  • computational studies leading to the synthesis of conformationally constrained bioactive peptides
  • spectrometric and spectroscopic studies of bioactive peptides
  • peptides with non-standard amino acid residues
  • design and synthesis of stapled peptides
  • cyclic and macrocyclic peptides, including analogues
  • new synthetic methodologies toward bioactive peptides
  • design and synthesis of peptidomimetics
  • design and synthesis of cell penetrating peptides
  • Synthesis of glycopeptides and peptide nucleic acid (PNAs)

Published Papers (2 papers)

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Research

16 pages, 3257 KiB  
Article
Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione
by Rezeda A. Ishkaeva, Ilyas S. Nizamov, Dmitriy S. Blokhin, Elizaveta A. Urakova, Vladimir V. Klochkov, Ilnar D. Nizamov, Bulat I. Gareev, Diana V. Salakhieva and Timur I. Abdullin
Molecules 2021, 26(10), 2973; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26102973 - 17 May 2021
Cited by 6 | Viewed by 2494
Abstract
Phosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts with nitrogen-containing biomolecules; however, their potential as a peptide modifier is poorly known. We synthesized amphiphilic ammonium salts of O,O-dimenthyl DTP with glutathione, [...] Read more.
Phosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts with nitrogen-containing biomolecules; however, their potential as a peptide modifier is poorly known. We synthesized amphiphilic ammonium salts of O,O-dimenthyl DTP with glutathione, a vital tripeptide with antioxidant, protective and regulatory functions. DTP moiety imparted radical scavenging activity to oxidized glutathione (GSSG), modulated the activity of reduced glutathione (GSH) and profoundly improved adsorption and electrooxidation of both glutathione salts on graphene oxide modified electrode. According to NMR spectroscopy and GC–MS, the dithiophosphates persisted against immediate dissociation in an aqueous solution accompanied by hydrolysis of DTP moiety into phosphoric acid, menthol and hydrogen sulfide as well as in situ thiol-disulfide conversions in peptide moieties due to the oxidation of GSH and reduction of GSSG. The thiol content available in dissolved GSH dithiophosphate was more stable during air oxidation compared with free GSH. GSH and the dithiophosphates, unlike DTP, caused a thiol-dependent reduction of MTS tetrazolium salt. The results for the first time suggest O,O-dimenthyl DTP as a redox modifier for glutathione, which releases hydrogen sulfide and induces biorelevant redox conversions of thiol/disulfide groups. Full article
(This article belongs to the Special Issue Design and Synthesis of Biologically Active Peptides)
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19 pages, 1887 KiB  
Article
Thrombin-Derived Peptides Potentiate the Activity of Gram-Positive-Specific Antibiotics against Gram-Negative Bacteria
by Charlotte M. J. Wesseling, Thomas M. Wood, Cornelis J. Slingerland, Kristine Bertheussen, Samantha Lok and Nathaniel I. Martin
Molecules 2021, 26(7), 1954; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26071954 - 30 Mar 2021
Cited by 6 | Viewed by 2504
Abstract
The continued rise of antibiotic resistance threatens to undermine the utility of the world’s current antibiotic arsenal. This problem is particularly troubling when it comes to Gram-negative pathogens for which there are inherently fewer antibiotics available. To address this challenge, recent attention has [...] Read more.
The continued rise of antibiotic resistance threatens to undermine the utility of the world’s current antibiotic arsenal. This problem is particularly troubling when it comes to Gram-negative pathogens for which there are inherently fewer antibiotics available. To address this challenge, recent attention has been focused on finding compounds capable of disrupting the Gram-negative outer membrane as a means of potentiating otherwise Gram-positive-specific antibiotics. In this regard, agents capable of binding to the lipopolysaccharide (LPS) present in the Gram-negative outer membrane are of particular interest as synergists. Recently, thrombin-derived C-terminal peptides (TCPs) were reported to exhibit unique LPS-binding properties. We here describe investigations establishing the capacity of TCPs to act as synergists with the antibiotics erythromycin, rifampicin, novobiocin, and vancomycin against multiple Gram-negative strains including polymyxin-resistant clinical isolates. We further assessed the structural features most important for the observed synergy and characterized the outer membrane permeabilizing activity of the most potent synergists. Our investigations highlight the potential for such peptides in expanding the therapeutic range of antibiotics typically only used to treat Gram-positive infections. Full article
(This article belongs to the Special Issue Design and Synthesis of Biologically Active Peptides)
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