Preparation of species-selective MetAP inhibitors activated by peptide deformylase
| Project/Area Number |
15K05567
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bio-related chemistry
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| Research Institution | Saga University |
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Principal Investigator |
OSADA Satoshi 佐賀大学, 理工学部, 准教授 (50284609)
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| Co-Investigator(Kenkyū-buntansha) |
兒玉 浩明 佐賀大学, その他部局等, 理事 (80205418)
平 順一 九州工業大学, 大学院情報工学研究院, 助教 (20549612)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 酵素阻害剤 / メチオニン / メチオニンアミノペプチダーゼ / ペプチドデホルミラーゼ / ペプチドミミック / メチオニンアミノペプチダ ーゼ / 抗菌活性 |
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| Outline of Final Research Achievements |
Methionine aminopeptidase (MetAP) which concerning protein maturation is involved in almost all species, and it is necessary to create species-selective MetAP inhibitors to the use as antimicrobials. In this study, we aimed at the action mechanism to be activated by bacterial-specific peptide deformylase (PDF) to release a MetAP inhibitor. Therefore, PDF activation of the formylated derivative of the existing substrate mimic type inhibitor candidates and the synthesis of the compound containing the MetAP inhibitory unit recognized in PDF were attempted. The results of enzyme assay showed that the compounds containing an oxadiazole ring are promising as peptide mimics that can be recognized by PDF and can inhibit MetAP.
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| Academic Significance and Societal Importance of the Research Achievements |
創薬には副作用の低減のために選択性の向上が求められるが，選択性の高さは狭い適用範囲の医薬品となるトレードオフの問題がある。本研究ではタンパク質合成酵素阻害剤をバクテリア選択的な阻害剤として設計するのではなく，候補となる阻害剤をバクテリア特有の酵素で活性化させる作用機序による選択性の発現を目指して阻害剤の分子設計を行った。異なる２種の酵素に認識される構造要件を探索することは困難ではあるが，病態に関連する酵素を複数狙った相乗効果をもつ薬剤の分子設計にも適用できるものと期待できる。
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Report
(5 results)
Research Products
(10 results)
