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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Veröffentlicht in:Angewandte Chemie International Edition 2015-07, Vol.54 (31), p.8896-8927
Hauptverfasser: Pelay-Gimeno, Marta, Glas, Adrian, Koch, Oliver, Grossmann, Tom N.
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container_issue 31
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container_title Angewandte Chemie International Edition
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creator Pelay-Gimeno, Marta
Glas, Adrian
Koch, Oliver
Grossmann, Tom N.
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. A matter of class: Inhibitors of protein–protein interactions can be obtained by mimicking peptide binding epitopes in their bioactive conformation. For this purpose, several strategies have been evolved to yield molecules that are generally referred to as peptidomimetics. This Review highlights these approaches and introduces a new classification for peptidomimetics that enables a clear assignment of available approaches.
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subjects Analogies
Binding
Binding sites
Biocompatibility
Classification
Epitopes - chemistry
Evolution
Inhibitors
Models, Molecular
Peptides
Peptides - chemistry
peptidomimetics
Peptidomimetics - pharmacology
Protein Interaction Domains and Motifs - genetics
Protein Structure, Secondary
protein-protein interactions
Proteins
Review
Signal Transduction
Strategy
title Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes
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