Original Research Novel X-linked inhibitor of apoptosis protein inhibitors as probes of apoptosis in biology and medicine

We report here a series of new inhibitors of the X-linked inhibitor of apoptosis protein (XIAP protein) based on the SMAC-tetrapeptide AVPI. The structural novelty of these molecules is the presence of the proline mimetic exo-2-azabicyclo[2.2.1]heptane-3-carboxylic acid, leading to analogs with similar activity to the natural ligand peptide. The structure–activity relationship and computational docking studies support the convenience of this unnatural amino acid as a building block to develop new peptides or small molecules targeting the XIAP-BIR3 domain