Development of a new foldamer as a mimetic of alfa-helix

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15476
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Hokkaido University
• Principal Investigator: WATANABE Mizuki 北海道大学, 薬学研究院, 講師 (20507173)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: ペプチドミメティクス / 配座制御 / フォルダマー

Outline of Final Research Achievements

I designed of optically active cyclopropane δ-amino acid oligomers wth various stereochemistries and calculated their most stable conformation using MacroModel. As a result, a homo-oligomers of specific stereoisomer of an optically active cyclopropane δ-amino acid form stable, right-handed helix. Then, I synthesized the optically active cyclopropane δ-amino acid monomer from the optically active glycidol via a stereoselective Grignard reaction and an asymmetric alkylation using asymmetric auxiliary groups in 18 steps. After oligomerization to various lengths, CD measurement, NMR measurement, and X-ray crystal structure analysis of the three-dimensional structure were performed. As a result, it was found that a hexameric or higher oligomer forms a helical secondary structure as calculated.

Free Research Field

創薬化学

Academic Significance and Societal Importance of the Research Achievements

タンパク質間相互作用の制御を狙ったペプチドミメティクスの開発研究は盛んになされているものの、普遍的な方法論といえるものが確立されているわけではない。本研究は、様々なタンパク質間相互作用に適用可能な一般性の高い新規ペプチドミメティクス開発方法論を提示・実践するものである。本研究の成果は、タンパク質間相互作用を標的としたペプチドミメティクス創薬の新たな基盤として発展する可能性を秘める。