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Special Issue "Peptides in Chemical Biology and Drug Discovery"

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

Deadline for manuscript submissions: 31 May 2019

Special Issue Editors

Guest Editor
Assoc. Prof. Steven L. Cobb

Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK
Website 1 | Website 2 | E-Mail
Interests: chemical-biology of peptides; organic synthesis; peptide and peptoid chemistry; bio-organic fluorine chemistry; bio-conjugation; drug target validation; infectious disease and neglected tropical diseases
Guest Editor
Dr. Albert Isidro-Llobet

GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, United Kingdom
Website | E-Mail
Interests: peptide synthesis; organic chemistry; chemical biology; drug discovery; medicinal chemistry; drug target validation; peptide therapeutics; green chemistry

Special Issue Information

Dear Colleagues,

Peptides are biological molecules with wide-ranging applications in the fields of both chemical biology and drug discovery. Peptides can provide valuable tools for the interrogation of complex biological and cellular process, and naturally occurring peptides often provide inspiration for the design and development of novel drug candidates against a wide range of diseases.

Advances in synthetic methodology (e.g., stapling and cyclisation strategies) and site-selective amino acid modification and conjugation have greatly aided in the development of peptides in many of the aforementioned areas. For example, advances in peptide bio-conjugation strategies have helped design new systems for targeted intracellular drug delivery. Similarly, new cyclisation strategies have allowed more complex peptide scaffolds to be accessed and have also helped researchers overcome the inherently poor pharmacokinetic properties associated with many peptides.

Recent advances in the application of peptides and peptide-based systems in the fields of chemical biology and drug discovery are welcomed for inclusion in this Special Issue for Molecules.

Assoc. Prof. Steven L. Cobb
Dr. Albert Isidro-Llobet
Guest Editors

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 papers will be 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 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). 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

  • Peptide synthesis
  • Peptide natural products
  • Peptide based drug delivery
  • Synthesis of novel amino acids
  • Site-selective peptide modification
  • Peptide bio-conjugation strategies
  • Peptide stapling and cyclisation
  • Peptide inhibitors of protein-protein interactions
  • Peptide therapeutics
  • Peptide drug conjugates
  • Peptide ligands in PROTAC design

Published Papers (2 papers)

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Research

Open AccessFeature PaperArticle d-Amino Acid Pseudopeptides as Potential Amyloid-Beta Aggregation Inhibitors
Molecules 2018, 23(9), 2387; https://doi.org/10.3390/molecules23092387
Received: 8 August 2018 / Revised: 6 September 2018 / Accepted: 14 September 2018 / Published: 18 September 2018
PDF Full-text (6873 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A causative factor for neurotoxicity associated with Alzheimer’s disease is the aggregation of the amyloid-β (Aβ) peptide into soluble oligomers. Two all d-amino acid pseudo-peptides, SGB1 and SGD1, were designed to stop the aggregation. Molecular dynamics (MD) simulations have been carried out
[...] Read more.
A causative factor for neurotoxicity associated with Alzheimer’s disease is the aggregation of the amyloid-β (Aβ) peptide into soluble oligomers. Two all d-amino acid pseudo-peptides, SGB1 and SGD1, were designed to stop the aggregation. Molecular dynamics (MD) simulations have been carried out to study the interaction of the pseudo-peptides with both Aβ13–23 (the core recognition site of Aβ) and full-length Aβ1–42. Umbrella sampling MD calculations have been used to estimate the free energy of binding, ∆G, of these peptides to Aβ13–23. The highest ∆Gbinding is found for SGB1. Each of the pseudo-peptides was also docked to Aβ1–42 and subjected up to seven microseconds of all atom molecular dynamics simulations. The resulting structures lend insight into how the dynamics of Aβ1–42 are altered by complexation with the pseudo-peptides and confirmed that SGB1 may be a better candidate for developing into a drug to prevent Alzheimer’s disease. Full article
(This article belongs to the Special Issue Peptides in Chemical Biology and Drug Discovery)
Figures

Graphical abstract

Open AccessArticle Identification of Nucleophilic Probes for Protease-Mediated Transpeptidation
Molecules 2018, 23(9), 2109; https://doi.org/10.3390/molecules23092109
Received: 30 July 2018 / Revised: 16 August 2018 / Accepted: 20 August 2018 / Published: 22 August 2018
PDF Full-text (3045 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Proteases have evolved to mediate the hydrolysis of peptide bonds but may perform transpeptidation in the presence of a proper nucleophilic molecule that can effectively compete with water to react with the acyl-enzyme intermediate. There have been several examples of protease-mediated transpeptidation, but
[...] Read more.
Proteases have evolved to mediate the hydrolysis of peptide bonds but may perform transpeptidation in the presence of a proper nucleophilic molecule that can effectively compete with water to react with the acyl-enzyme intermediate. There have been several examples of protease-mediated transpeptidation, but they are generally inefficient, and little effort has been made to systematically control the transpeptidation activity of other proteases with good nucleophiles. Here, we developed an on-bead screening approach to find a probe that functions efficiently as a nucleophile in the protease-mediated transpeptidation reaction, and we identified good probes for a model protease DegP. These probes were covalently linked to the C-termini of the cleaved peptides in a mild condition and made the selective enrichment of ligated peptides possible. We suggest that good nucleophilic probes can be found for many other proteases that act via acyl-enzyme intermediates, and these probes will help characterize their substrates. Full article
(This article belongs to the Special Issue Peptides in Chemical Biology and Drug Discovery)
Figures

Figure 1

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: D-amino acid pseudopeptides as potential amyloid-beta aggregation inhibitors
Authors: B. Mehrazma, S. K. A. Opare, A. Petoyan, A. Rauk*
Affiliation: Department of Chemistry; University of Calgary; Calgary AB, Canada T2N 1N4, Canada
Email:
Abstract: A causative factor for neurotoxicity associated with Alzheimer’s disease is the aggregation of the amyloid-β (Aβ) peptide into soluble oligomers. Two all D-amino acid pseudo-peptides, SGB1 and SGD1, were designed to stop the aggregation. Molecular dynamics (MD) simulations have been carried out to study the interaction of the pseudo-peptides with both Aβ13-23 (the core recognition site of Aβ) and full-length Aβ1-42. Umbrella sampling MD calculations have been used to estimate the free energy of binding, ∆G, of these peptides to Aβ13-23. The highest ∆Gbinding is found for SGB1. Each of the pseudo-peptides were also docked to Aβ1-42 and subjected up to two microseconds of all atom molecular dynamics simulations. The resulting structures lend insight into how the dynamics of Aβ1-42 are altered by complexation with the pseudo-peptides.

Title: Peptide-Based Nanoparticles for Optimizing Drug Delivery
Author: Kunchi Zhang
Affiliation: Shanghai University of Medicine & Health Sciences, Shanghai, China
Email:
Abstract: Peptide-based nanoparticles are innovative well-defined nanoplatforms with the advantages of biocompatibility, low toxicity, high loading capacity and structural diversity. Applications of peptide-based nanoparticles in various fields have been explored, especially in tumor treatment. This review gives an overview of the latest studies on engineering peptide-based nanoparticles as drug delivery for the enhanced cancer therapy, including the chemotherapy, gene therapy, photothermal therapy, photodynamic therapy, and the multimodality therapy. The opportunities and challenges in this field are also been discussed.

Title: Development of cupper electrodes modified with bimetallic deposits: Application as sensors of cysteine rich peptides synthetized by tobacco cells exposed to cytotoxic levels of cadmium
Authors: Patricio Espinoza-Montero; Marjorie Montero-Jimenez; Carlos Fernando Velasco Medina and Lenys Mercedes Fernandez Martinez
Affiliation: Escuela de Ciencias Químicas, Pontificia Universidad Católica del Ecuador, Avenida 12 de Octubre and Roca, Apartado 17-01-2184, Quito, Ecuador
Email:
Abstract: Pollution in plants due to heavy metal exposure is recognized as a serious environmental problem, so in recent years the promotion of new technologies capable of detect heavy metals on field has been a priority. This paper presents an electrochemical sensor development capable of diagnosing heavy metal pollution through cysteine rich peptides detection in plants. First, a cupper electrode was modified with a nafion film, and bimetallic deposits of Ag-Hg or Ag-Bi were sheltered, to replace Hg as traditionally employed electrodes. The sensors electrodic surfaces were characterized by Scanning Electron Microscopy, Cyclic Voltammetry and Electrochemical Impedance Spectroscopy. The electrodes were used in cysteine and glutathione monitoring, as model peptides that plants release when pollution of heavy metals is present and applied in real samples of Nicotiana tabacum cells exposed to cytotoxic levels of cadmium. Micrographs showed scattered evenly particles in the nafion film, with an approximate diameter of 150 µm. The Ag-Hg and Ag-Bi electrodes exhibit similarly results, with glutathione detection limits of 2.62 µmol L-1 and 5.53 µmol L-1 respectively. Despite the complex matrix where cells were grown, the electrodes were capable of direct detection of synthetized peptides, so they are candidates for sensors applicable to field sampling.
Keywords: Brdička Reaction, Electrochemical Detection, Cysteine Rich Peptides, Bimetallic Deposits.

Title: Evaluation of Cadmium Pollution in Cellular Extracts of Tamarillo (Solanum Betaceum) Cultivatd “in vitro”, by Indtrect Electrochemical Detection of Cysteine-Rich Peptides
Authors: Patricio Espinoza-Montero; Marjorie Montero-Jimenez; Carlos Fernando Velasco Medina and Lenys Mercedes Fernandez Martinez
Affiliation: Escuela de Ciencias Químicas, Pontificia Universidad Católica del Ecuador, Avenida 12 de Octubre and Roca, Apartado 17-01-2184, Quito, Ecuador
Email:
Abstract: Tamarillo is a plant of great local consumption, however, is not known if it is able to bioaccumulate cadmium, the problem is that cadmium can be transferred to humans through the food chain, which has toxic effects. The accumulation of Cd(II) by tamarillo (Solanum betaceum) cells was evaluated through the detection of cysteine-rich peptides. It was used the method of electrochemical generation of iodine. These compounds are synthesized in the plant when it is contaminated by metals. The cells were cultivated, the method was evaluated and finally it was determined the concentration of cysteine rich-peptides in the cell cultures with Cd(II). Cells grow from explants of stems in Murashige and Skoog (MS) medium supplemented with 30 g L-1 of sugar and 1 mg L-1 of 2,4-D. The calibration curve obtained indicates a linear range from 0 to 250 µmol L-1, with a detection limit of 4.82 µmol L-1 (3.3 s/m). The concentration of peptides in cell suspensions increases with the CdSO4 concentration and the exposure time. The results indicate that tamarillo cells accumulate cadmium. During with 5 days of exposure and 100 µmol L-1 CdSO4, the cells of the suspension still do not suffer from apoptosis. The proposed method shows useful characteristics for monitoring heavy metals in growing plants.
Keywords: cadmium pollution, electrochemical detection, cysteine-rich peptides, tamarillo.

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