Non-peptidic anti-aids agents: Inhibition of HIV-1 proteinase by disulfonates

Brinkworth R.I. and Bairlie D.P. (1992) Non-peptidic anti-aids agents: Inhibition of HIV-1 proteinase by disulfonates. Biochemical and Biophysical Research Communications, 188 2: 624-630. doi:10.1016/0006-291X(92)91102-V

Author Brinkworth R.I.
Bairlie D.P.
Title Non-peptidic anti-aids agents: Inhibition of HIV-1 proteinase by disulfonates
Journal name Biochemical and Biophysical Research Communications   Check publisher's open access policy
ISSN 1090-2104
Publication date 1992-10-30
Sub-type Article (original research)
DOI 10.1016/0006-291X(92)91102-V
Volume 188
Issue 2
Start page 624
End page 630
Total pages 7
Subject 1303 Specialist Studies in Education
1304 Biophysics
1312 Molecular Biology
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import
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Created: Tue, 14 Jun 2016, 01:23:42 EST by System User