Title: A Modular Approach to HIV-1 Proteinase Inhibitor Design
Abstract: HIV-1 proteinase represents a promising target for antiviral chemotherapy. We have designed, synthesized, and tested modular inhibitors combining an active-site inhibitor tethered to a structure targeted to the dimerization domain of the enzyme. At pH 5 the parent active site inhibitor, the equimolar mixture of active site and dimerization inhibitors, and the best compound from our series of modular inhibitors show the same inhibition activity. At neutral pH, however, the combination of the dimerization and active-site inhibitors shows a synergistic effect. Moreover, the modular inhibitor has an IC50value 5× lower than the parent active site inhibitor and 2× lower than the equimolar mixture of the two parent inhibitors. The Lineweaver-Burk plot for modular inhibitors corresponds to a pattern for mixed type inhibition.
Publication Year: 1996
Publication Date: 1996-05-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
Access and Citation
Cited By Count: 18
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