Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

Protein–protein interactions (PPIs) are involved at all levels of cellular organization, thus making the development of PPI inhibitors extremely valuable. The identification of selective inhibitors is challenging because of the shallow and extended nature of PPI interfaces. Inhibitors can be obtaine...

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Main Authors: Pelay-Gimeno, Marta, Glas, Adrian, Koch, Oliver, Grossmann, Tom N
Format: Online
Language:English
Published: WILEY-VCH Verlag 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557054/
id pubmed-4557054
recordtype oai_dc
spelling pubmed-45570542015-09-08 Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes Pelay-Gimeno, Marta Glas, Adrian Koch, Oliver Grossmann, Tom N Review Protein–protein interactions (PPIs) are involved at all levels of cellular organization, thus making the development of PPI inhibitors extremely valuable. The identification of selective inhibitors is challenging because of the shallow and extended nature of PPI interfaces. Inhibitors can be obtained by mimicking peptide binding epitopes in their bioactive conformation. For this purpose, several strategies have been evolved to enable a projection of side chain functionalities in analogy to peptide secondary structures, thereby yielding molecules that are generally referred to as peptidomimetics. Herein, we introduce a new classification of peptidomimetics (classes A–D) that enables a clear assignment of available approaches. Based on this classification, the Review summarizes strategies that have been applied for the structure-based design of PPI inhibitors through stabilizing or mimicking turns, β-sheets, and helices. WILEY-VCH Verlag 2015-07-27 2015-06-26 /pmc/articles/PMC4557054/ /pubmed/26119925 http://dx.doi.org/10.1002/anie.201412070 Text en © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Pelay-Gimeno, Marta
Glas, Adrian
Koch, Oliver
Grossmann, Tom N
spellingShingle Pelay-Gimeno, Marta
Glas, Adrian
Koch, Oliver
Grossmann, Tom N
Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes
author_facet Pelay-Gimeno, Marta
Glas, Adrian
Koch, Oliver
Grossmann, Tom N
author_sort Pelay-Gimeno, Marta
title Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes
title_short Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes
title_full Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes
title_fullStr Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes
title_full_unstemmed Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes
title_sort structure-based design of inhibitors of protein–protein interactions: mimicking peptide binding epitopes
description Protein–protein interactions (PPIs) are involved at all levels of cellular organization, thus making the development of PPI inhibitors extremely valuable. The identification of selective inhibitors is challenging because of the shallow and extended nature of PPI interfaces. Inhibitors can be obtained by mimicking peptide binding epitopes in their bioactive conformation. For this purpose, several strategies have been evolved to enable a projection of side chain functionalities in analogy to peptide secondary structures, thereby yielding molecules that are generally referred to as peptidomimetics. Herein, we introduce a new classification of peptidomimetics (classes A–D) that enables a clear assignment of available approaches. Based on this classification, the Review summarizes strategies that have been applied for the structure-based design of PPI inhibitors through stabilizing or mimicking turns, β-sheets, and helices.
publisher WILEY-VCH Verlag
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557054/
_version_ 1613471788862275584

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