Elucidation of pharmacological effects of antibiotics against genetic diseases caused by nonsense mutations and development of new therapeutic agents
| Project/Area Number |
26860025
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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 |
Physical pharmacy
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| Research Institution | Sophia University |
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Principal Investigator |
Kondo Jiro 上智大学, 理工学部, 准教授 (10546576)
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| Research Collaborator |
Hanessian Stephen モントリオール大学, 教授
Baasov Timor テクニオン・イスラエル工科大学, 教授
Ennifar Eric フランス国立科学研究機構, 研究部長
Auffinger Pascal フランス国立科学研究機構, 研究部長
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ナンセンス変異型遺伝性疾患 / 抗生物質 / リボソーム / Ｘ線結晶解析 / ドラッグデザイン |
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| Outline of Final Research Achievements |
In order to develop new therapeutic agents against genetic diseases, I have performed structural studies of the ribosomal RNA molecular switches of several different organisms/cells by X-ray analysis and have designed and synthesized new drug compounds based on the obtained structural data. We have succeeded to design and synthesize several compounds possessing high readthrough, antiprotozoal or antibacterial activity and less toxicity against human. Especially, one of the designed/synthesized fluorinated aminoglycosides specifically binds to the RNA molecular switches of eukaryote and antibiotic-resistant bacteria. This compound can be a potent therapeutic agent against genetic diseases caused by nonsense mutations.
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Toxicity modulation, resistance enzyme evasion, and A-site X-ray structure of broad-spectrum antibacterial neomycin analogs2014
Author(s)
Juan Pablo Maianti, Hiroki Kanazawa, Paola Dozzo, Rowena D. Matias, Lee Ann Feeney, Eliana S. Armstrong, Darin J. Hildebrandt, Timothy R. Kane, Micah J. Gliedt, Adam A. Goldblum, Martin S. Linsell, James B. Aggen, Jiro Kondo, Stephen Hanessian.
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Journal Title
ACS Chemical Biology
Volume: 9
Issue: 9
Pages: 2067-2073
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Synthesis, broad spectrum antibacterial activity, and X-ray co-crystal structure of the decoding bacterial ribosomal A-site with 4'-deoxy-4'-fluoro neomycin analogs2014
Author(s)
Stephen Hanessian, Oscar M. Saavedra, Miguel A. Vilchis-Reyes, Juan P. Maianti, Hiroki Kanazawa, Paola Dozzo, Rowena D. Matias, Alisa Serio, Jiro Kondo.
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Journal Title
Chemical Science
Volume: 5
Issue: 12
Pages: 4621-4632
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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