Design and synthesis of a potent biotinylated Smac mimetic

A biotinylated Smac mimetic (2) was designed based upon our previously reported potent, conformationally constrained Smac mimetic (1). Smac mimetic (2) was synthesized and determined to bind to XIAP protein with a high-affinity (Ki value of 13 nM) and is therefore a useful pharmacological tool for probing the intracellular targets of this class of potent Smac mimetics.