| Project/Area Number |
17K15484
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Kyoto Pharmaceutical University (2019)
Tokyo University of Pharmacy and Life Science (2017-2018) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | フォリスタチン / マイオスタチン阻害 / 構造活性相関 / マイオスタチン阻害ペプチド / 選択的阻害 / 生体分子 |
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| Outline of Final Research Achievements |
Myostatin is a negative regulatory factor against muscular mass. Myostatin inhibition is one of the promising strategies for the treatment of muscle atrophic diseases. Follistatin is well known as a myostatin inhibitory protein, and the N-terminal domain interacts with the type-I receptor binding site of myostatin. We focused on this interaction and synthesized a series of fragment peptides to explore a new inhibitory peptide. Consequently, 14-mer peptides was successfully identified and the important residues for effective inhibition was clarified. Injected intramuscularly, this peptide significantly increased muscle mass to 112% in mice. Also, structure activity relationship study afforded a new derivative with selectively enhanced myostatin inhibitory activity.
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| Academic Significance and Societal Importance of the Research Achievements |
マイオスタチン阻害剤は、世代縦断的に広範な筋萎縮疾患への適用が期待できる。例えば、がん悪液質、筋ジストロフィー、寝たきり患者などでみられる廃用性筋萎縮、老年性の筋萎縮（サルコペニア）等の克服に応用できる可能性がある。また、マイオスタチン阻害は脂肪細胞の肥大化を抑制するとの報告があり、肥満（メタボリック症候群）に奏功する可能性も秘めていることも興味深い。更にペプチドは、抗体に比べると比較的安価に化学合成可能であり、経済的メリットもある。
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