HIV-1 protease inhibitors: Ketomethylene isosteres with unusually high affinity compared with hydroxyethylene isostere analogs

Aime Marinier, Mihaly V. Toth, Kathryn Houseman, Richard Mueller, Garland R. Marshall

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

HIV protease is a member of the aspartic proteinase family of proteolytic enzymes which include pepsin and renin. In contrast to the enhanced affinity seen with renin and pepsin upon conversion of the transition-state isostere, ketomethylene, to the hydroxyethylene, a set of HIV protease inhibitors showed a reduction in affinity. This implies that interactions with the active site of other segments of the inhibitor than those of the transition-state analog must predominate in the case of HIV protease, and that observations made on mammalian aspartic proteinases do not necessarily apply to viral aspartic proteinases.

Original languageEnglish
Pages (from-to)919-925
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume2
Issue number9
DOIs
StatePublished - Sep 1994

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