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Publication

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

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.

Publication date
September 1, 1994
Principal Investigators
Marinier A, Toth MV, Houseman K, Mueller R, Marshall GR
PubMed reference
Bioorg. Med. Chem. 1994;2(9):919-25
PubMed ID
7712127
Affiliation
Department of Moelcular Biology and Pharmacology, Washington University, St. Louis, MO 63130.