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- W2047382199 abstract "Based upon an earlier observation that sodium docosanedioate (NaO2C-(CH2)20-CO2Na) weakly inhibits HIV-1 proteinase (IC50 12μM), we have identified a class of more potent inhibitors (sulfonic acids) of this enzyme which are likewise dianionic at pH 5–6.5. Many of the compounds were moderately strong inhibitors of the enzyme (IC50 40nM-10μM) and some have previously been shown to have anti-HIV activity in lymphocytes. Proteinase inhibition was dependent on the separation between sulfonate/carboxylate substituents, consistent with the hypothesis that negative charged ends of an inhibitor might form ionic bonds with Arg 8 and Arg 108 located at either end of the substrate-binding groove of the enzyme. The binding mode remains to be established by structure elucidation. Results for enzyme inhibition are presented along with structure-activity relationships and evidence for pH dependent inhibition. The general observations reported here may be useful for developing more potent and selective non-peptidic proteinase inhibitors." @default.
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- W2047382199 date "1992-10-01" @default.
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- W2047382199 title "Non-peptidic anti-aids agents: Inhibition of HIV-1 proteinase by disulfonates" @default.
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- W2047382199 doi "https://doi.org/10.1016/0006-291x(92)91102-v" @default.
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