Inhibition of HIV-1 Protease by Oxim Derivatives
| Autor: | Shuichi Miyamoto, Takashi Nishigaki, Ryuichi Yagi, Hiroshi Handa, Yasuko Ishikawa, Tomoaki Komai, Atsushi Kasuya, Hisayo Suzuki-Sunagawa |
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| Rok vydání: | 1997 |
| Předmět: |
Models
Molecular Molecular model medicine.medical_treatment Biophysics HIV Infections Binding Competitive Biochemistry Substrate Specificity Cell-free system law.invention HIV-1 protease law Aspartic Acid Proteases medicine Humans HIV Protease Inhibitor Moiety Molecular Biology Protease Cell-Free System biology Chemistry Hydrolysis HIV Protease Inhibitors Cell Biology Ketones Molecular biology Chronic Disease HIV-1 Recombinant DNA biology.protein |
| Zdroj: | Biochemical and Biophysical Research Communications. 230:557-561 |
| ISSN: | 0006-291X |
| Popis: | In cell-free proteolytic processing using recombinant HIV-1 protease and Gag precursor polypeptide, certain simple oxim derivatives containing halogenomethylketone and phenyl moieties displayed HIV-1 protease inhibitory activity. Their Ki values ranged from 2.1 microM to 6.3 microM and they did not inhibit significantly other aspartic acid proteases. Both the halogenomethylketone moiety and the oxim structure were essential for the observed inhibition. Molecular modeling analysis suggested that these compounds are recognized by the HIV-1 protease as the P1 and P1' part of the substrate. In addition, one potent derivative showed inhibition of viral maturation in HIV-1IIIB chronically infected Molt-4 cells. These results indicate that it is possible to develop new and specific nonpeptidyl HIV protease inhibitors of low molecular weight. |
| Databáze: | OpenAIRE |
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