Targeting Peptide-mediated Interactions in Omics.

Peptide-mediated interactions (PMIs) play a crucial role in cell signaling network, which are responsible for about half of cellular protein-protein associations in the human interactome and have recently been recognized as a new kind of promising druggable target for drug development and disease therapy. In this article, we give a systematic review regarding the proteome-wide discovery of PMIs and targeting druggable PMIs with chemical drugs, self-inhibitory peptides and protein agents, particularly focusing on their implications and applications for therapeutic purpose in omics. We also introduce computational peptidology strategies used to model, analyze and design PMI-targeted molecular entities and further extend the concepts of protein context, direct/indirect readout and enthalpy/entropy effect involved in PMIs. Current issues and future perspective on this topic are discussed. There is still a long way to go before establishment of efficient therapeutic strategies to target PMIs on the omics scale. This article is protected by copyright. All rights reserved.