Interfering peptides targeting protein-protein interactions: the next generation of drugs?
Heriberto Bruzzoni-Giovanelli1, Valerie Alezra2, Nicolas Wolff3
1Université 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.
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.
Related Concept Videos
Protein-protein Interfaces
Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Pharmacogenomics: Identification of New Drug Targets
Targeted Cancer Therapies
There are several types of targeted therapies against...
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Factors Affecting Protein-Drug Binding: Drug Interactions
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...


