2022 Fiscal Year Final Research Report
Chemical Basis and Medicinal Application of Alkene Dipeptide Isosteres
| Project/Area Number |
20H03363
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | Shizuoka University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 中分子ペプチド / 生物学的等価体 / アルケン / 非共有結合性相互作用 / β-ターン構造 / グアニン四重鎖構造 |
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| Outline of Final Research Achievements |
In order to elucidate the chemical basis and molecular properties of alkene-type dipeptide isosteres, we investigated the peptide bond mimicry of non-covalent interactions, including n-pi* interactions and hyperconjugative interactions, which are crucial for the structure formation and molecular recognitions of peptides. Our studies revealed that the steric and stereoelectronic effects derived from the substituents on the alkene moieties play an extremely important role in stabilizing the conformation of peptides, which is essential for the structure formation and molecular recognitions of peptides. Based on these findings, we successfully identified med-sized beta-turn peptides and peptidomimetics that can selectively bind to the guanine quadruplex structure.
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| Free Research Field |
創薬化学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の学術的意義は、中分子ペプチド創薬において有用なバイオイソスターであるアルケン型ペプチド結合等価体について、それぞれの等価体には化学的特徴や固有の機能があり, アルケン上の置換基が特性を決めることを明らかにした点にある。これは様々なパラドックスや活性低下が問題となっていたアルケン型ペプチド結合等価体の創薬応用において、その解決策と明確な設計指針を提供するものである。これらの知見は、中分子ペプチド創薬の加速化につながることから、社会的意義も高い。
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