Molecular mechanism of neuroprotective activity of geldanamycin

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K12743
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: Nagoya University
• Principal Investigator: NISHIKAWA Toshio 名古屋大学, 生命農学研究科, 教授 (90208158)
• Co-Investigator(Renkei-kenkyūsha): IMOTO Masaya 慶應義塾大学, 理工学部, 教授 (60213253)
• Research Collaborator: OSADA Hiroyuki 理化学研究所, 環境資源科学研究センター ケミカルバイオロジー研究グループ, グループディレクター (80160836) ; MUROI Makoto 理化学研究所, 環境資源科学研究センター ケミカルバイオロジー研究グループ, 専任研究員 (30261168)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: ゲルダナマイシン / 神経保護作用 / Hsp-90 / 標的同定 / ケミカルバイオロジー

Outline of Final Research Achievements

Geldamamycin (GA), a potent inhibitor of HSP-90, shows neuroprotective effect in a low concentration. We found that an analog that removed the carbamoyl group at the 7 position also show a potent neuroprotective activity. Thus the purpose of this research is to elucidate an unknown mechanism of this neuroprotective activity by GA. We synthesized two probe molecules which contains biotin-linker on the bais of SAR of DCGA. However,pull-down assay using this biotin-probes did not give any new proteins. Proteome analysis dose not shows the difference between GA and DCGA. Thus we concluded that the neuroprotective effect by GA is induced by its binding to HSP-90 although the binding is very weak.

Free Research Field

有機化学