Design and synthesis of a simplified inhibitor for XIAP-BIR3 domain

Bioorg Med Chem Lett. 2009 Nov 15;19(22):6413-8. doi: 10.1016/j.bmcl.2009.09.058. Epub 2009 Sep 17.

Abstract

Based on tetrapeptide AVPI, we were able to design and synthesize a new simplified scaffold to inhibit the BIR3 domain of the XIAP protein at low micromolar range. The uncomplicated synthesis and the binding activity of the molecule disclosed here represent an attractive alternative to develop new compounds targeting the protein-protein interaction of XIAP/caspase9.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis
  • Crystallography, X-Ray
  • Drug Design
  • Humans
  • Inhibitor of Apoptosis Proteins*
  • Mitochondrial Proteins
  • Oligopeptides / chemistry*
  • Protein Conformation
  • Protein Structure, Tertiary
  • Structure-Activity Relationship*
  • X-Linked Inhibitor of Apoptosis Protein / administration & dosage*
  • X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors

Substances

  • Inhibitor of Apoptosis Proteins
  • Mitochondrial Proteins
  • Oligopeptides
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human