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

Exp Biol Med (Maywood). 2011 Feb;236(2):247-51. doi: 10.1258/ebm.2010.010284.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Bridged Bicyclo Compounds / metabolism
  • Humans
  • Models, Molecular
  • Molecular Biology / methods*
  • Molecular Dynamics Simulation
  • Peptides / chemistry
  • Peptides / metabolism
  • Proline / analogs & derivatives
  • Structure-Activity Relationship
  • X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors*
  • X-Linked Inhibitor of Apoptosis Protein / metabolism*

Substances

  • 2-azabicyclo(2.2.1)heptane-3-carboxylic acid
  • Bridged Bicyclo Compounds
  • Peptides
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Proline