Mechanism of resistance to translocation defective reverse transcriptase inhibitors
| Project/Area Number |
23590636
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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 |
Applied pharmacology
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| Research Institution | Tohoku University |
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Principal Investigator |
ASHINO Yugo 東北大学, 医学(系)研究科(研究院), 准教授 (20361082)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Eiichi 東北大学, 大学院医学系研究科, 講師 (50271151)
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| Project Period (FY) |
2011-04-28 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | ウイルス / ＨＩＶ / 薬剤耐性 / 逆転写酵素 / 多剤耐性 / HIV |
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| Research Abstract |
A novel nucleoside reverse transcriptase (RT) inhibitor, 4'-ethynyl-2-fluoro-deoxyadenosine (EFdA) inhibits translocation activity of RT. To elucidate mechanism of the action in detail, resistant HIV-1 and -2 variants to EFdA were induced in vitro. M184I/V in the RT was identified as the primary mutation, while A158T and T165M/R were considered as the secondary mutations. M184I/V much reduced replication kinetics of HIV, but some of the secondary mutations improved the reduced replication. Data obtained from enzymatic assays with recombinant RT well supported those from viral assays. In this study, we provide crucial information of key amino aicds for tranlocation activity and of drug design for novel inhibitors.
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Report
(3 results)
Research Products
(27 results)
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[Journal Article] Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design.2013
Author(s)
Izumi K, Kawaji K, Miyamoto F, Shimane K, Shimura K, Sakagami Y, Hattori T, Watanabe K, Oishi S, Fujii N, Matsuoka M, Kaku M, Sarafianos SG, Kodama EN.
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Journal Title
Int J Biochem Cell Biol.
Volume: 45
Issue: 4
Pages: 908-915
DOI
Related Report
Peer Reviewed
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[Journal Article] Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant.2012
Author(s)
Michailidis E, Singh K, Ryan EM, Hachiya A, Ong YT, Kirby KA, Marchand B, Kodama EN, Mitsuya H, Parniak MA, Sarafianos SG.
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Journal Title
Cell Mol Biol (Noisy-le-grand).
Volume: 58
Pages: 187-195
DOI
Related Report
Peer Reviewed
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[Journal Article] HIV-1 reverse transcriptase (RT) polymorphism 172K suppresses the effect of clinically relevant drug resistance mutations to both nucleoside and non-nucleoside RT inhibitors.2012
Author(s)
Hachiya A, Marchand B, Kirby KA, Michailidis E, Tu X, Palczewski K, Ong YT, Li Z, Griffin DT, Schuckmann MM, Tanuma J, Oka S, Singh K, Kodama EN, Sarafianos SG.
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Journal Title
J Biol Chem.
Volume: 287
Issue: 35
Pages: 29988-29999
DOI
Related Report
Peer Reviewed
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[Journal Article] Distinct Clinical Features in Nontuberculous Mycobacterial Disease with or without Latent Tuberculosis Infection2012
Author(s)
Siddiqi UR, Chagan-Yasutan H, Nakajima C, Saitoh H, Ashino Y, Usami O, Shiratori B, Usuzawa M, Suzuki Y, Hattori T.
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Journal Title
The Tohoku Journal of Experimental Medicine
Volume: 226
Issue: 4
Pages: 313-319
DOI
NAID
ISSN
0040-8727, 1349-3329
Related Report
Peer Reviewed
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