Strategies for targeting protein-protein interactions with synthetic agents

(Chemical Equation Presented) The development of small-molecule modulators of protein-protein interactions is a formidable goal, albeit one that possesses significant potential for the discovery of novel therapeutics. Despite the daunting challenges, a variety of examples exists for the inhibition of two large protein partners with low-molecular-weight ligands. This review discusses the strategies for targeting protein-protein interactions and the state of the art in the rational design of molecules that mimic the structures and functions of their natural targets. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.