2. Academic Validation
  3. Demonstration of direct binding of cIAP1 degradation-promoting bestatin analogs to BIR3 domain: Synthesis and application of fluorescent bestatin ester analogs

Demonstration of direct binding of cIAP1 degradation-promoting bestatin analogs to BIR3 domain: Synthesis and application of fluorescent bestatin ester analogs

  • Bioorg Med Chem Lett. 2008 Jun 1;18(11):3354-8. doi: 10.1016/j.bmcl.2008.04.031.
Shinichi Sato 1,  Hiroshi Aoyama,  Hiroyuki Miyachi,  Mikihiko Naito,  Yuichi Hashimoto
Affiliations

Affiliation

  • 1 Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
PMID: 18448338 DOI: 10.1016/j.bmcl.2008.04.031
Abstract

Overexpression of cIAP1 correlates with resistance to radiotherapy and chemotherapy in various cancers. Recently, we reported that a class of bestatin ester analogs represented by MeBS (2) destabilized and promoted the degradation of cIAP1 through auto-ubiquitination, and thereby sensitized Cancer cells to Apoptosis. Herein, we present chemical evidence that bestatin ester analogs directly interact with the cIAP1-BIR3 domain by means of fluorescence polarization assay and photoaffinity labeling assay using fluorescent probes.

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