Development of new self-inactivating chaperon without side effects

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15391
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tottori University
• Principal Investigator: Nanba Eiji 鳥取大学, 生命機能研究支援センター, 教授 (40237631)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: シャペロン / ライソゾーム病 / ファブリー病 / ゴーシェ病 / 自己不活型

Outline of Final Research Achievements

We developed "self-inactivating novel chaperone" which undergoes structural change under acidic condition in lysosome and dissociates from target enzyme protein by conversion to inactive form. Based on the deoxynojirimycin (DGJ) compound, several candidate compounds were synthesized by adding an orthoester group. The structure of compounds changed by pH change. We studied the effect of these compounds for Fabry and Gaucher diseases using in vitro and cultured cells. As a result, we identified the compounds as original concept. The compounds did not show enzyme inhibition even when used at high concentrations.

Free Research Field

人類遺伝学　小児神経学