Inhibition of a prion conversion by suppressing protein fluctuations using small-molecules

2014 Fiscal Year Final Research Report

• Project/Area Number: 24570180
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biophysics
• Research Institution: Gifu University
• Principal Investigator: KAMATARI Yuji O. 岐阜大学, 生命科学総合研究支援センター, 助教 (70342772)
• Co-Investigator(Kenkyū-buntansha): KUWATA Kazuo 岐阜大学, 連合創薬医療情報研究科, 教授 (00170142) ; AKASAKA Kazuyuki 近畿大学, 先端技術総合研究所, 教授 (50025368) ; ODA Masayuki 京都府立大学, 生命環境科学研究科(系), 准教授 (20318231)
• Co-Investigator(Renkei-kenkyūsha): ISHIKAWA Takeshi 長崎大学, 医歯薬学総合研究科, 准教授 (80505909)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: プリオン蛋白質 / プリオン病 / 抗プリオン化合物 / 創薬 / 揺らぎ / 高圧 / 準安定状態 / 抗体

Outline of Final Research Achievements

Prion diseases are fatal neurodegenerative diseases, with no effective treatment. In this study, we firstly categories antiprion compounds and showed some compounds stabilized the native conformation. We then identified fluctuations in prion protein important for its conformational conversion using NMR spectroscopy. We also found new anti-prion compounds including RNA aptamer and tacrolimus. We lastly reviewed importance of cavities for protein function and evolution. This study indicated suppression of conformational fluctuations may be a useful strategy for drug development of neurodegenerative diseases. This study also indicated that a wide range of conformational space needed to be explored.

Free Research Field

生物物理学