2022 Fiscal Year Final Research Report
molecular design and action mechanism of peptidomimetics using natural products-like cubic scaffolds
| Project/Area Number |
20H02868
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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 37020:Chemistry and chemical methodology of biomolecules-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
石崎 敏理 大分大学, 医学部, 教授 (70293876)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | ペプチドミメティクス / 活性発現の分子機構 / 生体機能物質 / 医薬品探索 |
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| Outline of Final Research Achievements |
From a unique peptide mimetic library of about 200 compounds owned by Oita University, several fibrosis-inhibiting compounds were identified through anti-fibrotic in vitro screening using cells. PTSA and ITC experiments revealed that some of these compounds bind to a specific subtype of PPIase. A similar fibrosis inhibition was confirmed by knockdown of this PPIase subtype. Furthermore, in a bleomycin-induced pulmonary fibrosis mouse model, alleviation of symptoms was observed with three compounds. These results have successfully found compounds with preventive/therapeutic effects on pulmonary fibrosis among about 200 types of compounds. We have succeeded in discovering a promising new chemical space for drug candidate compounds.
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| Free Research Field |
創薬化学
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| Academic Significance and Societal Importance of the Research Achievements |
切れ味の鋭い生理活性物質の発見は生命科学の飛躍的な進歩に貢献してきたが、天然資源が枯渇している近年は新規物質の発見が困難となっており、天然物化学の従来法に代わる新しい探索手法の開発が望まれている。本研究では、生理活性ペプチドやタンパク質の部分構造から新しい低分子を設計・合成することで得られる化合物のライブラリから、医薬品のシードとして有望な複数の化合物をスクリーニングにより見出すことができることを示した。枯渇する天然資源に変わって、新規の有望なケミカルスペースを提供する方法論として、ペプチドミメティクスの有用性を示すことができた。
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