2010 Fiscal Year Final Research Report

Development of novel regulators for controlling glutathione biosynthesis

Research Project

Project/Area Number	21810015
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Living organism molecular science
Research Institution	Kyoto University
Principal Investigator	WATANABE Bunta Kyoto University, 化学研究所, 助教 (10544637)
Research Collaborator	HIRATAKE Jun 京都大学, 化学研究所, 教授 (80199075) HIBI Takao 福井県立大学, 生物資源学部, 教授 (00285181)
Project Period (FY)	2009 – 2010
Keywords	有機科学 / 酵素反応 / グルタチオン / 感染症 / 化学療法剤 / ドラッグデザイン
Research Abstract	This research is aimed to develop novel antiinfective drugs using (2S)-2-amino-4-(2-carboxybutylsulfonimidoyl) butyric acid, a potent γ-glutamylcysteine synthetase (γ-GCS) inhibitor, as a precursor. Hydrophobic amino acids were conjugated to N-terminal of the lead compound. The synthetic prodrugs significantly decreased glutathione content of E. coli as compared to the precursor. This result suggested that 1) these prodrugs were uptaken into E.coli and decomposed by peptidases, and 2) the liberated inhibitor inactivated E.coli γ-GCS in situ.

(1 results)