Cargando…
Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches
Protein–protein interfaces play fundamental roles in the molecular mechanisms underlying pathophysiological pathways and are important targets for the design of compounds of therapeutic interest. However, the identification of binding sites on protein surfaces and the development of modulators of pr...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178479/ https://www.ncbi.nlm.nih.gov/pubmed/37175549 http://dx.doi.org/10.3390/ijms24097842 |
_version_ | 1785040873831006208 |
---|---|
author | Monti, Alessandra Vitagliano, Luigi Caporale, Andrea Ruvo, Menotti Doti, Nunzianna |
author_facet | Monti, Alessandra Vitagliano, Luigi Caporale, Andrea Ruvo, Menotti Doti, Nunzianna |
author_sort | Monti, Alessandra |
collection | PubMed |
description | Protein–protein interfaces play fundamental roles in the molecular mechanisms underlying pathophysiological pathways and are important targets for the design of compounds of therapeutic interest. However, the identification of binding sites on protein surfaces and the development of modulators of protein–protein interactions still represent a major challenge due to their highly dynamic and extensive interfacial areas. Over the years, multiple strategies including structural, computational, and combinatorial approaches have been developed to characterize PPI and to date, several successful examples of small molecules, antibodies, peptides, and aptamers able to modulate these interfaces have been determined. Notably, peptides are a particularly useful tool for inhibiting PPIs due to their exquisite potency, specificity, and selectivity. Here, after an overview of PPIs and of the commonly used approaches to identify and characterize them, we describe and evaluate the impact of chemical peptide libraries in medicinal chemistry with a special focus on the results achieved through recent applications of this methodology. Finally, we also discuss the role that this methodology can have in the framework of the opportunities, and challenges that the application of new predictive approaches based on artificial intelligence is generating in structural biology. |
format | Online Article Text |
id | pubmed-10178479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101784792023-05-13 Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches Monti, Alessandra Vitagliano, Luigi Caporale, Andrea Ruvo, Menotti Doti, Nunzianna Int J Mol Sci Review Protein–protein interfaces play fundamental roles in the molecular mechanisms underlying pathophysiological pathways and are important targets for the design of compounds of therapeutic interest. However, the identification of binding sites on protein surfaces and the development of modulators of protein–protein interactions still represent a major challenge due to their highly dynamic and extensive interfacial areas. Over the years, multiple strategies including structural, computational, and combinatorial approaches have been developed to characterize PPI and to date, several successful examples of small molecules, antibodies, peptides, and aptamers able to modulate these interfaces have been determined. Notably, peptides are a particularly useful tool for inhibiting PPIs due to their exquisite potency, specificity, and selectivity. Here, after an overview of PPIs and of the commonly used approaches to identify and characterize them, we describe and evaluate the impact of chemical peptide libraries in medicinal chemistry with a special focus on the results achieved through recent applications of this methodology. Finally, we also discuss the role that this methodology can have in the framework of the opportunities, and challenges that the application of new predictive approaches based on artificial intelligence is generating in structural biology. MDPI 2023-04-25 /pmc/articles/PMC10178479/ /pubmed/37175549 http://dx.doi.org/10.3390/ijms24097842 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Monti, Alessandra Vitagliano, Luigi Caporale, Andrea Ruvo, Menotti Doti, Nunzianna Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches |
title | Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches |
title_full | Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches |
title_fullStr | Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches |
title_full_unstemmed | Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches |
title_short | Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches |
title_sort | targeting protein–protein interfaces with peptides: the contribution of chemical combinatorial peptide library approaches |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178479/ https://www.ncbi.nlm.nih.gov/pubmed/37175549 http://dx.doi.org/10.3390/ijms24097842 |
work_keys_str_mv | AT montialessandra targetingproteinproteininterfaceswithpeptidesthecontributionofchemicalcombinatorialpeptidelibraryapproaches AT vitaglianoluigi targetingproteinproteininterfaceswithpeptidesthecontributionofchemicalcombinatorialpeptidelibraryapproaches AT caporaleandrea targetingproteinproteininterfaceswithpeptidesthecontributionofchemicalcombinatorialpeptidelibraryapproaches AT ruvomenotti targetingproteinproteininterfaceswithpeptidesthecontributionofchemicalcombinatorialpeptidelibraryapproaches AT dotinunzianna targetingproteinproteininterfaceswithpeptidesthecontributionofchemicalcombinatorialpeptidelibraryapproaches |