2023 Fiscal Year Final Research Report
Development and regulation of peptide secondary structures using side-chain stapling
Project/Area Number |
20K06967
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
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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)
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Project Period (FY) |
2020-04-01 – 2024-03-31
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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 |
E- and Z-selective ring-closing metatheses of peptides with 4-allyloxy-L-proline were achieved. Furthermore, ring-closing metathesis of peptides between five-membered carbocyclic alpha,alpha-disubstituted alpha-amino acids possessing allyl-tether resulted in high E-selectivities with a >20:1 ratio, while that between (S)-(4-pentenyl)alanines resulted in poor selectivities of approx 2imately:1. The synthesized peptides were subjected to epoxidation of alpha,beta-unsaturated ketone as an organocatalyst, and excellent enantioselectivities up to 99% ee were observed.
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Free Research Field |
薬系化学
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Academic Significance and Societal Importance of the Research Achievements |
ペプチドは生体内でも重要な役割を担うため、その物性と機能の解明は重要である。しかし、既存のペプチド側鎖上での閉環メタセシス反応はE/Z混合物を与えていた。今回人工のアミノ酸を組み込むことで、EまたはZ選択性を発現させることに成功できた。またそのペプチドのX線結晶構造はα-ヘリックスを示しており、生体内でペプチドの作用点の多くがα-ヘリックスを形成していることから、今後の展開が期待される。
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