| Project/Area Number |
12557219
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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 | 展開研究 |
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| Research Field |
医薬分子機能学
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| Research Institution | Kumamoto University |
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Principal Investigator |
OTSUKA Masami Kumamoto University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (40126008)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASAKI Tetsuo Kumamoto University, Graduate School of Pharmaceutical Sciences, Research Associate, 大学院・薬学研究科, 助手 (60182474)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | artificial ligand / AIDS virus / NFkB / HIV-EP1 / Sp1 / peptide nucleic acids / HIV-EPl / Spl |
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| Research Abstract |
The Long Terminal Repeat, the promoter region of the AIDS provirus contains a tandem kB sequence, three consecutive GC boxes, and a TATA box. Proteins NFkB, HIV-EP1 and Sp1 specifically bind to these sequences and paticipate in the transcription amf replicatiom of AIDS virus. The present research aimed at proteins and nucleic acids, i. e., the inhibition of the functions of these transcriptional proteins and the design of DNA-cleaving agents targeting the Long Terminal Repeat
Sp1 and HIV-EP1 is a zinc finger proteins containing zinc in their DNA recognition-binding sites. We prepared various pyridine-based zinc chelators to inactivate these proteims by abstracting zinc. We synthesized biphenyl-type metal chelators with an aromatic substituent on the pyridine, considering the enzyme binding. In particular, a compound with a naphthyl group showed excellent inhibitory activity against a zinc protein.
We carried out a molecular design of novel peptide nucleic acid for the specific recognition of the DNA sequence of HIV provirus. We prepared optically active monomer constituents and the corresponding oligomer of peptide nucleic acids containing a glycyl-b-alanine backbone starting with D-and L-aspartic acids.
Thus, the results of the present research include the successful design of novel metal chelators that inhibit the function of zinc proteins and development of a novel peptide nucleic acid that could target the DNA of AIDS provirus.
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