Peptides and Peptidomimetics as Tools to Probe Protein-Protein Interactions – Disruption of HIV-1 gp41 Fusion Core and Fusion Inhibitor Design

Abstract

Protein-protein interactions play important roles in many critical processes in the life sciences, such as signal transduction, lipid membrane fusion, receptor recognition, etc., and many of them are important targets for drug development and design (Wilson 2009; Tavassoli 2011). Unlike an enzyme-substrate interaction which usually has a deep binding pocket in the protein for substrate binding, protein-protein interactions usually involve a large interacting interface; as a result, it is a big challenge for small molecule drugs to efficiently competitively occupy the interface and disrupt protein-protein interactions that modulate these life processes. Proteins are natural ligands that can modulate protein-protein interactions; however, they are not ideal therapeutic agents because of their expensive production costs and the fact that they are not able to be administered orally. In proteinprotein interactions, energy is not always equally distributed throughout the binding interface; a couple of focused areas may account for the main protein-protein interaction energy, called a hot spot, which can be the target for a small molecule protein-protein interaction inhibitor (PPII).