title: Demonstration of direct binding of cIAP1 degradation-promoting bestatin analogs to BIR3 domain: Synthesis and application of fluorescent bestatin ester analogs.
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.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyachi
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Naito
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D017209:Apoptosis / Q000187:drug effects*; D005454:Fluorescence Polarization; D051034:Inhibitor of Apoptosis Proteins / Q000737:chemistry / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007931:Leucyl Aminopeptidase / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D019920:Photoaffinity Labels / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D054875:Ubiquitination / Q000187:drug effects*
chemical_list: D051034:Inhibitor of Apoptosis Proteins; C529718:MeBS compound; D019920:Photoaffinity Labels; D000626:Aminopeptidases; D007931:Leucyl Aminopeptidase; C019721:aminopeptidase B; D007930:Leucine; C012211:ubenimex