Protein Secondary Structure Mimetics as Modulators of Protein–Protein and Protein–Ligand Interactions•

The development of low-molecular-weight agents that modulate protein–protein interactions has been regarded as a difficult goal due to the relatively large and featureless protein interfacial surfaces involved [1–3]. Conventional methods for identifying inhibitors of protein–protein interactions generally involve the preparation and screening of large chemical libraries to discover lead compounds [4]. Despite significant advances in high-throughput methods, screening a large number of compounds cannot guarantee the delivery of potential drug candidates with necessary potency and selectivity. Structure-based design is an area of much current interest and represents a much-considered alternative to the identification of molecules that reproduce structural and functional features of protein interfaces. In this chapter, we will review some representative studies of using synthetic agents that mimic protein secondary structures in drug discovery, in particular, to target protein–protein and protein–ligand interactions. These studies have expanded the horizon of drug design, strengthened our understanding of protein–protein and protein–ligand interactions, and offered an economical alternative to conventional screening methods.