Peptide based Molecules as Protein-Protein Interaction Inhibitors: Tools for Chemical Genetics and Therapy

Siddhartha      Roy; Piya      Ghosh; Neeladri      Sekhar Roy; Abhishek      Mazumder; Koushik      Roy; Asit      Kumar Manna; Shampa      Mallick; Israr      Ahmed

Abstract

Protein-protein interaction networks play a central role in a large number of cellular processes. Interaction networks are regulated to a large extent through post-translational modifications. The underlying causes of many diseases are found in defective protein-protein interactions and the resulting dysregulated signaling. Study and inhibition of proteinprotein interaction networks are thus crucial to the understanding of physiological and disease processes. Small molecules so far have been the mainstay as chemical genetic and therapeutic tools. Inherent instability, low plasma half-life and other characteristics of peptides have so far prevented their widespread use in chemical genetics and therapy. However, recent developments have removed many of the drawbacks in use of peptides within cells and in organisms; as a consequence, peptides are poised to take a new leap as a promising class of molecules for use in chemical genetics and therapeutics. In this article we review recent developments in this area. We discuss methods for developing peptides that bind a given target. We also explore the use of peptides for targeting to organs and organelles. Due to modular nature of functionalities within a peptide, different functionalities can be combined in a peptide with relative ease. This characteristic, combined with biocompatible nature of the entity make future of peptides bright as therapeutic agents.

Keywords: Helix, homing, inhibition, mimetics, peptide, protein-protein interaction, targeting, therapeutics, Protein-protein interaction inhibitors, phagemid genome, repA sequence, multiple cyclic metallopeptide modules