Peptide Design to Control Protein-protein Interactions

Overview

Journal Chem Soc Rev

Date 2025 Jan 16

PMID 39817557

Authors

Suzanne P van Wier

Andrew M Beekman

Affiliations

Soon will be listed here.

Abstract

Targeting of protein-protein interactions has become of huge interest in every aspect of medicinal and biological sciences. The control of protein interactions selectively offers the opportunity to control biological processes while limiting off target effects. This interest has massively increased with the development of cryo-EM and protein structure prediction with tools such as RosettaFold and AlphaFold. When designing molecules to control protein interactions, either inhibition or stabilisation, a starting point is commonly peptide design. This tutorial review describes that process, highlighting the selection of an initial sequence with and without structural information. Subsequently, methods for how the sequence can be analysed for key residues and how this information can be used to optimise the ligand efficiency are highlighted. Finally a discussion on how peptides can be further modified to increase their affinity and cell permeability, improving their drug-like properties, is presented.

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