Secondary structure analysis of peptides having alpha-(trifluoromethyl)amino acids and its approach to medicinal chemistry
| Project/Area Number |
17K19495
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmaceutical Sciences and related fields
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| Research Institution | Nagasaki University |
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Principal Investigator |
TANAKA Masakazu 長崎大学, 医歯薬学総合研究科(薬学系), 教授 (00227175)
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| Project Period (FY) |
2017-06-30 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 有機化学 / 生体分子 / 薬学 / 分子認識 / ペプチド / タンパク質 / ２次構造 / 蛋白質 |
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| Outline of Final Research Achievements |
The optical resolution method of racemic α-trifluoromethyl (αCF3)-amino acids using chiral BINOL esters was developed. Also, we synthesized several chiral phase-transfer catalysts derived from quinidine. Using a chiral phase-transfer catalyst, we synthesized an optically active αCF3-amino acid with 78% ee. We synthesized diastereomeric two peptides Cbz-(L-Leu)2-{(S)- or (R)-CF3-Aib}-(L-Leu)2-OMe, and studied the preferred conformation of peptides using 1H NMR and CD spectra, and also X-ray crystallographic analysis.
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| Academic Significance and Societal Importance of the Research Achievements |
トリフルオロメチル(α-CF3)化された化合物は、医薬品の探索研究において重要である。しかし、光学活性なα-CF3-アミノ酸を導入したペプチドについての研究は限られていた。今回、α-CF3-アミノ酸の光学活性体の合成法を開発し、光学活性な(S)-あるいは(R)-α-CF3-アラニン（SとRは光学活性体の鏡像体を意味する）をL-ロイシン中に導入したペプチドの立体構造を調べたところ、導入する鏡像体によりペプチドC末側の立体構造に違いが見られることが分かった。
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Report
(5 results)
Research Products
(12 results)
