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 (dPMIs) with chemical drugs, self-inhibitory peptides (SIPs) 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.