1991 Fiscal Year Final Research Report Summary
Deveropment of the Anti-AIDS Drug Based on the Aspartyl Protease Inhbitor
| Project/Area Number |
02670952
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
FUNAKOSHI Susumu Kyoto University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (10135593)
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| Co-Investigator(Kenkyū-buntansha) |
IBUKA Toshiroh Kyoto Univ. Faculty of Pharm. Sciences, Associate Professor, 薬学部, 助教授 (80025692)
OTAKA Akira Kyoto Univ. Faculty of Pharm. Sciences, Research Associate, 薬学部, 助手 (20201973)
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| Project Period (FY) |
1990 – 1991
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| Keywords | AIDS Virus / Aspartyl protease / Inhibitor / organocopper-Lewis Acid Complex / Trans olefin type isostere / Fmoc-Based Solid Phase Synthesis |
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| Research Abstract |
Sequences of various proteins are encoded in the RNA of AIDS virus and they are realized in their target cells and then constructive proteins and enzymes which help viruses be differentiated and grow are produced.
Among them the existence of an enzyme was pointed out, which processes a protein playing an essential role in the viruses differentiation and multiplication.
This enzyme is aspartic protease having aspartic acid at its active center. It is pointed out that the replacement of the proposed active site Asp-25 with Asn, eliminate the infectivity of the virus.
Our study aimes to synthesize this enzyme chemically to investigate its characteristics and to plan its inhibitor so that the medicine to cure the AJDS will be able to be developed. As for the development of the inhibitor, the general synthesis of trans-olefine type dipeptide-isostere.
1)Organocupper-Lewis acid complex developed by the reporters was applied to homochiral CL, P -enoate, 1, 3chirality transfer reaction was performed, and it was proved that the aimed basic structure, (E)-alken isosteric dipeptide, can be obtained highly selectively at high yield. Some sorts of trans-olefine type isosteres were synthesized.
2)When the aspartyl protease was synthesized by Fmoc-based solid phase synthesis, the chemoselectively purification technique developed by the reporters was proved to be very effective for the purification of protein consisted of 99 amino acid residues synthesized by solid phase technique.
By this study, trans-alkene dipeptide-isostere, which has been considered to be hardly synthesized because of many functional groups, was synthesized and its highly efficient and stereoselective synthesis was established.
This method can be applied to the synthesis of inhibiting peptides against HIV protease produced with the Isester.
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Research Products
(8 results)
