Development of Mirror-Image Screening Systems for XIAP BIR3 Domain Inhibitors

Bioconjug Chem. 2019 May 15;30(5):1395-1404. doi: 10.1021/acs.bioconjchem.9b00154. Epub 2019 Apr 17.


The X-linked inhibitor of apoptosis protein baculovirus IAP repeat (XIAP BIR3) domain is a promising therapeutic target for cancer treatment. For the mirror-image screening campaign to identify drug candidates from an unexplored mirror-image natural product library, a facile synthetic protocol for XIAP BIR3 domain synthesis was established by a native chemical ligation strategy using conserved cysteines present among BIR domains. The native and mirror-image XIAP BIR3 domains with an appropriate functional group for labeling were prepared using the established protocol. Taking advantage of the resulting synthetic proteins, several bioassay systems were developed to characterize inhibitors of the protein-protein interaction between the XIAP BIR3 domain and the second mitochondria-derived activator of caspases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biological Assay
  • Humans
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Protein Folding
  • Sequence Homology, Amino Acid
  • X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors*
  • X-Linked Inhibitor of Apoptosis Protein / chemistry
  • X-Linked Inhibitor of Apoptosis Protein / metabolism


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