Design and synthesis of peptide foldamer using alpha,alpha-disubstituted alpha-amino acids

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14870
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Nagasaki University
• Principal Investigator: UEDA Atsushi 長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (10732315)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ジ置換アミノ酸 / ペプチド / 有機分子触媒 / 薬学 / 有機化学

Outline of Final Research Achievements

Synthesis of α,α-disubstituted α-amino acids and their peptides were performed. Secondary structural analysis of these peptides could be useful for design of peptide foldamers. α-Trifluoromethylated α,α-disubstituted α-amino acids were synthesized with a variety of side chains. Optical resolution of these amino acids were achieved by chromatographic separation of the corresponding (R)-BINOL ester derivative. We also synthesized α-amino acids possessing rare sugar on their side chain. Simplification of peptide catalyst structure resulted in high catalytic activity, which is important from the point of green sustainability.

Free Research Field

化学系薬学

Academic Significance and Societal Importance of the Research Achievements

生体内で重要な役割を担うペプチドは、機能性分子としての高いポテンシャルを有している。今回フッ素を導入したペプチドにより、バイオアベイラビリティーの増大が期待でき、また一方で、希少糖を導入したアミノ酸を今後ペプチドへ導入していくことで、生体内リガンドとしての可能性も高まる。ペプチド触媒の簡素化による触媒活性の向上は、化合物のロスを減らし、グリーンサスティナビリティの向上に資する結果と考えられる。