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Brinkworth RI, Fairlie DP. Non-peptidic anti-AIDS agents: inhibition of HIV-1 proteinase by disulfonates. Biochem Biophys Res Commun. 1992;188(2):624-30doi: 10.1016/0006-291x(92)91102-v.
Brinkworth, R. I., & Fairlie, D. P. (1992). Non-peptidic anti-AIDS agents: inhibition of HIV-1 proteinase by disulfonates. Biochemical and biophysical research communications, 188(2), 624-30. https://doi.org/10.1016/0006-291x(92)91102-v
Brinkworth, R I, and Fairlie, D P. "Non-peptidic anti-AIDS agents: inhibition of HIV-1 proteinase by disulfonates." Biochemical and biophysical research communications vol. 188,2 (1992): 624-30. doi: https://doi.org/10.1016/0006-291x(92)91102-v
Brinkworth RI, Fairlie DP. Non-peptidic anti-AIDS agents: inhibition of HIV-1 proteinase by disulfonates. Biochem Biophys Res Commun. 1992 Oct 30;188(2):624-30. doi: 10.1016/0006-291x(92)91102-v. PMID: 1445307.
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Biochem Biophys Res Commun. 1992 Oct 30;188(2):624-30. doi: 10.1016/0006-291x(92)91102-v.

Non-peptidic anti-AIDS agents: inhibition of HIV-1 proteinase by disulfonates.

Biochemical and biophysical research communications

R I Brinkworth, D P Fairlie

Affiliations

  1. Centre for Drug Design and Development, University of Queensland, Brisbane, Australia.

PMID: 1445307 DOI: 10.1016/0006-291x(92)91102-v

Abstract

Based upon an earlier observation that sodium docosanedioate (NaO2C-(CH2)20-CO2NA) weakly inhibits HIV-1 proteinase (IC50 12 microM), 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-10 microM) 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.

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