| Project/Area Number |
11672173
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
SHOJI Shozo Kumamoto University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60040317)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAMUNE Nobutoki Kumamoto University, Faculty of Pharmaceutical Sciences, Research associate, 薬学部, 助手 (60322749)
MISUMI Shogo Kumamoto University, Faculty of Pharmaceutical Sciences, Research associate, 薬学部, 助手 (40264311)
古石 和親 熊本大学, 薬学部, 助手 (40238663)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | HIV-1 / PROTEASE / p2gag / INHERENT SUICIDE PEPTIDE |
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| Research Abstract |
In late years, it is reported that patient life was prolonged by the spread of HAART therapy. However, an appearance of multiple drug resistance virus complicates chemotherapy of AIDS with difficulty of compliance and adverse drug actions by the long term dosage of antiviral agent. Development of anti-HIV agents of the next generation that is overcoming problems of drug resistance is demanded, because HIV-1 immediately acquires the ability of drug resistance.
HIV-1 protease generates viral structural proteins and various kinds of enzymes (protease, reverse transcriptase, integrase) from a precursor protein (Pr55^<gag>, p160^<gag-pol>). But, little is known what inhibits the proteolytic activity of HIV-1 protease after it has completed processing.
We pay attention to this point and get the following study results till now.
5) The synthetic p2^<gag> peptide inhibits the proteolytic activity of HIV-1 protease in vitro. Furthermore, the nonapeptide (AEAMSQVTN) derived from N-terminus of p2^<gag> peptide exhibits a potent inhibitory action of HIV-1 protease.
2) p2^<gag> domain is highly conserved in various HIV-1 subtypes.
3) It was determined by exclusion gel chromatography that HIV-1 protease after treatment of the synthetic p2^<gag> peptide dissociated from the active dimeric form to an inactive monomeric form.
4) Actually, p2^<gag> peptide was detected in HIV-1 viral particles using MALDI TOF-MS.
5) Some lead compounds were found by mimicing of p2^<gag> peptide.
These results suggests that p2^<gag> peptide is found to be an inherent suicide inhibitor of HIV-1 protease and may play an important role in overcoming problems of the multiple drug-resistant form of HIV-1.
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