The chemical biology of apoptosis. Exploring protein-protein interactions and the life and death of cells with small molecules.

Apoptosis, a fundamental process for both human health and disease, is initiated and regulated by protein-protein interactions, notable examples of which are the interactions involving Bcl-2 and IAP protein families. This article discusses recent advances in the use of chemical approaches in discovering and studying small molecules targeted to proteins of the Bcl-2 and IAP families. These small molecules and their complexes with receptors provide the tools and model systems to probe the basic mechanism of molecule recognition underling the life and death of cells and develop novel strategies for therapeutic intervention of the dysregulated apoptotic process. The review of these studies highlights the opportunity and challenge in this emerging area of chemical and chemical biological research.