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Drug Discov Today. 2018 Feb;23(2):272-285. doi: 10.1016/j.drudis.2017.10.016. Epub 2017 Oct 31.

Interfering peptides targeting protein-protein interactions: the next generation of drugs?

Author information

1
Université Paris 7 Denis Diderot, Université Sorbonne Paris Cité, Paris, France; UMRS 1160 Inserm, Paris, France; Centre d'Investigation Clinique 1427 Inserm/AP-HP Hôpital Saint Louis, Paris, France.
2
Université Paris-Sud, Laboratoire de Méthodologie, Synthèse et Molécules Thérapeutiques, ICMMO, UMR 8182, CNRS, Université Paris-Saclay, Faculté des Sciences d'Orsay, France.
3
Unité de Résonance Magnétique Nucléaire des Biomolécules, CNRS, UMR 3528, Institut Pasteur, F-75015 Paris, France.
4
Université Paris 7 Denis Diderot, Université Sorbonne Paris Cité, Paris, France; ITODYS, UMR 7086 CNRS, Paris, France.
5
Université Paris 7 Denis Diderot, Université Sorbonne Paris Cité, Paris, France; Inserm UMR-S 973, RPBS, Paris, France.
6
CIMI Paris, UPMC, Inserm U1135, Hôpital Pitié Salpétrière, Paris, France. Electronic address: angelita.rebollo@upmc.fr.

Abstract

Protein-protein interactions (PPIs) are well recognized as promising therapeutic targets. Consequently, interfering peptides (IPs) - natural or synthetic peptides capable of interfering with PPIs - are receiving increasing attention. Given their physicochemical characteristics, IPs seem better suited than small molecules to interfere with the large surfaces implicated in PPIs. Progress on peptide administration, stability, biodelivery and safety are also encouraging the interest in peptide drug development. The concept of IPs has been validated for several PPIs, generating great expectations for their therapeutic potential. Here, we describe approaches and methods useful for IPs identification and in silico, physicochemical and biological-based strategies for their design and optimization. Selected promising in-vivo-validated examples are described and advantages, limitations and potential of IPs as therapeutic tools are discussed.

PMID:
29097277
DOI:
10.1016/j.drudis.2017.10.016
[Indexed for MEDLINE]

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