Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Current Advances in Peptide Inhibitors
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Current Advances in Peptide Inhibitors

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (25 March 2024) | Viewed by 6456

Special Issue Editor

Dr. Mirja Harms

E-Mail Website
Guest Editor
Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 4/M26 (ZQB) 3.106, 89081 Ulm, Germany
Interests: peptides; drug discovery; drug development; GPCRs; chemokines; immune modulation; inflammation; cancer

Special Issue Information

Dear Colleagues,

Peptide drugs have attracted increased attention over the last few years and have now reached the market for the treatment of a wide range of diseases, such as diabetes, cancer, and inflammatory diseases. This Special Issue will focus on the newest developments in the field of peptide-based therapeutics. This includes the discovery of novel peptide inhibitors from nature and other sources and their characterization and optimization for therapeutic applications. Manuscripts covering novel methods for peptide chemistry and modifications, rational drug design, as well as drug delivery systems are welcome. In addition, we will focus on new pharmaceutical targets and major breakthroughs in peptide biology.

Dr. Mirja Harms
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • peptides
  • peptide inhibitors
  • drug development
  • peptide modifications
  • PK/PD
  • delivery
  • endogenous peptide inhibitors

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

12 pages, 9259 KiB  
Article
Conformational States of the CXCR4 Inhibitor Peptide EPI-X4—A Theoretical Analysis
by Christoph Karsten Jung, Jan Münch and Timo Jacob
Int. J. Mol. Sci. 2023, 24(22), 16229; https://doi.org/10.3390/ijms242216229 - 12 Nov 2023
Viewed by 820
Abstract
EPI-X4, an endogenous peptide inhibitor, has exhibited potential as a blocker of CXCR4—a G protein-coupled receptor. This unique inhibitor demonstrates the ability to impede HIV-1 infection and halt CXCR4-dependent processes such as tumor cell migration and invagination. Despite its promising effects, a comprehensive [...] Read more.
EPI-X4, an endogenous peptide inhibitor, has exhibited potential as a blocker of CXCR4—a G protein-coupled receptor. This unique inhibitor demonstrates the ability to impede HIV-1 infection and halt CXCR4-dependent processes such as tumor cell migration and invagination. Despite its promising effects, a comprehensive understanding of the interaction between EPI-X4 and CXCR4 under natural conditions remains elusive due to experimental limitations. To bridge this knowledge gap, a simulation approach was undertaken. Approximately 150,000 secondary structures of EPI-X4 were subjected to simulations to identify thermodynamically stable candidates. This simulation process harnessed a self-developed reactive force field operating within the ReaxFF framework. The application of the Two-Phase Thermodynamic methodology to ReaxFF facilitated the derivation of crucial thermodynamic attributes of the EPI-X4 conformers. To deepen insights, an ab initio density functional theory calculation method was employed to assess the electrostatic potentials of the most relevant (i.e., stable) EPI-X4 structures. This analytical endeavor aimed to enhance comprehension of the inhibitor’s structural characteristics. As a result of these investigations, predictions were made regarding how EPI-X4 interacts with CXCR4. Two pivotal requirements emerged. Firstly, the spatial conformation of EPI-X4 must align effectively with the CXCR4 receptor protein. Secondly, the functional groups present on the surface of the inhibitor’s structure must complement the corresponding features of CXCR4 to induce attraction between the two entities. These predictive outcomes were based on a meticulous analysis of the conformers, conducted in a gaseous environment. Ultimately, this rigorous exploration yielded a suitable EPI-X4 structure that fulfills the spatial and functional prerequisites for interacting with CXCR4, thus potentially shedding light on new avenues for therapeutic development. Full article
(This article belongs to the Special Issue Current Advances in Peptide Inhibitors)
►▼ Show Figures

Figure 1

23 pages, 5347 KiB  
Article
Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet
by Louisa Filipe Rosa, Andreas Rings, Iris Stolzer, Louis Koeninger, Jan Wehkamp, Julia Beisner, Claudia Günther, Peter Nordkild, Benjamin A. H. Jensen and Stephan C. Bischoff
Int. J. Mol. Sci. 2023, 24(18), 13878; https://doi.org/10.3390/ijms241813878 - 9 Sep 2023
Cited by 1 | Viewed by 1500
Abstract
Obesity and metabolic comorbidities are associated with gut permeability. While high-fructose and Western-style diet (WSD) disrupt intestinal barrier function, oral administration of human α-defensin 5 (HD5) and β-defensin 2 (hBD2) is believed to improve intestinal integrity and metabolic disorders. Eighty-four male C57BL/6J mice [...] Read more.
Obesity and metabolic comorbidities are associated with gut permeability. While high-fructose and Western-style diet (WSD) disrupt intestinal barrier function, oral administration of human α-defensin 5 (HD5) and β-defensin 2 (hBD2) is believed to improve intestinal integrity and metabolic disorders. Eighty-four male C57BL/6J mice were fed a WSD or a control diet (CD) ± fructose (F) for 18 weeks. In week 13, mice were randomly divided into three intervention groups, receiving defensin fragment HD51–9, full-length hBD2, or bovine serum albumin (BSA)-control for six weeks. Subsequently, parameters of hepatic steatosis, glucose metabolism, and gut barrier function were assessed. WSDF increased body weight and hepatic steatosis (p < 0.01) compared to CD-fed mice, whereas peptide intervention decreased liver fat (p < 0.05) and number of hepatic lipid droplets (p < 0.01) compared to BSA-control. In addition, both peptides attenuated glucose intolerance by reducing blood glucose curves in WSDF-fed mice. Evaluation of gut barrier function revealed that HD51–9 and hBD2 improve intestinal integrity by upregulating tight junction and mucin expression. Moreover, peptide treatment restored ileal host defense peptides (HDP) expression, likely by modulating the Wnt, Myd88, p38, and Jak/STAT pathways. These findings strongly suggest that α- and β-defensin treatment improve hepatic steatosis, glucose metabolism, and gut barrier function. Full article
(This article belongs to the Special Issue Current Advances in Peptide Inhibitors)
►▼ Show Figures

Figure 1

20 pages, 7850 KiB  
Article
Inhibition of Pertussis Toxin by Human α-Defensins-1 and -5: Differential Mechanisms of Action
by Carolin Kling, Anja Sommer, Yasser Almeida-Hernandez, Armando Rodríguez, Julio A. Perez-Erviti, Rajendra Bhadane, Ludger Ständker, Sebastian Wiese, Holger Barth, Mario Pupo-Meriño, Arto T. Pulliainen, Elsa Sánchez-García and Katharina Ernst
Int. J. Mol. Sci. 2023, 24(13), 10557; https://doi.org/10.3390/ijms241310557 - 23 Jun 2023
Viewed by 1417
Abstract
Whooping cough is a severe childhood disease, caused by the bacterium Bordetella pertussis, which releases pertussis toxin (PT) as a major virulence factor. Previously, we identified the human antimicrobial peptides α-defensin-1 and -5 as inhibitors of PT and demonstrated their capacity to [...] Read more.
Whooping cough is a severe childhood disease, caused by the bacterium Bordetella pertussis, which releases pertussis toxin (PT) as a major virulence factor. Previously, we identified the human antimicrobial peptides α-defensin-1 and -5 as inhibitors of PT and demonstrated their capacity to inhibit the activity of the PT enzyme subunit PTS1. Here, the underlying mechanism of toxin inhibition was investigated in more detail, which is essential for developing the therapeutic potential of these peptides. Flow cytometry and immunocytochemistry revealed that α-defensin-5 strongly reduced PT binding to, and uptake into cells, whereas α-defensin-1 caused only a mild reduction. Conversely, α-defensin-1, but not α-defensin-5 was taken up into different cell lines and interacted with PTS1 inside cells, based on proximity ligation assay. In-silico modeling revealed specific interaction interfaces for α-defensin-1 with PTS1 and vice versa, unlike α-defensin-5. Dot blot experiments showed that α-defensin-1 binds to PTS1 and even stronger to its substrate protein Gαi in vitro. NADase activity of PTS1 in vitro was not inhibited by α-defensin-1 in the absence of Gαi. Taken together, these results suggest that α-defensin-1 inhibits PT mainly by inhibiting enzyme activity of PTS1, whereas α-defensin-5 mainly inhibits cellular uptake of PT. These findings will pave the way for optimization of α-defensins as novel therapeutics against whooping cough. Full article
(This article belongs to the Special Issue Current Advances in Peptide Inhibitors)
►▼ Show Figures

Figure 1

13 pages, 2016 KiB  
Article
Identification and Characterization of Three New Antimicrobial Peptides from the Marine Mollusk Nerita versicolor (Gmelin, 1791)
by Armando Rodriguez, Ernesto M. Martell-Huguet, Melaine González-García, Daniel Alpízar-Pedraza, Annia Alba, Antonio A. Vazquez, Mark Grieshober, Barbara Spellerberg, Steffen Stenger, Jan Münch, Ann-Kathrin Kissmann, Frank Rosenau, Ludger A. Wessjohann, Sebastian Wiese, Ludger Ständker and Anselmo J. Otero-Gonzalez
Int. J. Mol. Sci. 2023, 24(4), 3852; https://doi.org/10.3390/ijms24043852 - 14 Feb 2023
Cited by 6 | Viewed by 2168
Abstract
Mollusks have been widely investigated for antimicrobial peptides because their humoral defense against pathogens is mainly based on these small biomolecules. In this report, we describe the identification of three novel antimicrobial peptides from the marine mollusk Nerita versicolor. A pool of [...] Read more.
Mollusks have been widely investigated for antimicrobial peptides because their humoral defense against pathogens is mainly based on these small biomolecules. In this report, we describe the identification of three novel antimicrobial peptides from the marine mollusk Nerita versicolor. A pool of N. versicolor peptides was analyzed with nanoLC-ESI-MS-MS technology, and three potential antimicrobial peptides (Nv-p1, Nv-p2 and Nv-p3) were identified with bioinformatical predictions and selected for chemical synthesis and evaluation of their biological activity. Database searches showed that two of them show partial identity to histone H4 peptide fragments from other invertebrate species. Structural predictions revealed that they all adopt a random coil structure even when placed near a lipid bilayer patch. Nv-p1, Nv-p2 and Nv-p3 exhibited activity against Pseudomonas aeruginosa. The most active peptide was Nv-p3 with an inhibitory activity starting at 1.5 µg/mL in the radial diffusion assays. The peptides were ineffective against Klebsiella pneumoniae, Listeria monocytogenes and Mycobacterium tuberculosis. On the other hand, these peptides demonstrated effective antibiofilm action against Candida albicans, Candida parapsilosis and Candida auris but not against the planktonic cells. None of the peptides had significant toxicity on primary human macrophages and fetal lung fibroblasts at effective antimicrobial concentrations. Our results indicate that N. versicolor-derived peptides represent new AMP sequences and have the potential to be optimized and developed into antibiotic alternatives against bacterial and fungal infections. Full article
(This article belongs to the Special Issue Current Advances in Peptide Inhibitors)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop