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

Shinichi Sato; Hiroshi Aoyama; Hiroyuki Miyachi; Mikihiko Naito; Yuichi Hashimoto

doi:10.1016/j.bmcl.2008.04.031

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. Epub 2008 Apr 15.

Authors

Shinichi Sato¹, Hiroshi Aoyama, Hiroyuki Miyachi, Mikihiko Naito, Yuichi Hashimoto

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminopeptidases / antagonists & inhibitors
Apoptosis / drug effects*
Fluorescence Polarization
Inhibitor of Apoptosis Proteins / chemistry
Inhibitor of Apoptosis Proteins / metabolism*
Leucine / analogs & derivatives*
Leucine / chemical synthesis
Leucine / chemistry
Leucine / pharmacology
Leucyl Aminopeptidase / antagonists & inhibitors
Molecular Structure
Photoaffinity Labels / pharmacology
Tumor Cells, Cultured
Ubiquitination / drug effects*

Substances

Inhibitor of Apoptosis Proteins
MeBS compound
Photoaffinity Labels
Aminopeptidases
Leucyl Aminopeptidase
aminopeptidase B
Leucine
ubenimex