Development of a microtiter plate fluorescent assay for inhibition studies on the HTLV-1 and HIV-1 proteinases.
The proteinase of human T-cell leukemia virus type-1 (HTLV-1), similar to the proteinase of human immunodeficiency virus type-1 (HIV-1), is a potential target for chemotherapy, since the virus is associated with a number of human diseases. A microtiter plate fluorescent assay was developed for the HTLV-1 and HIV-1 proteinases for direct comparison of the inhibition profiles of the enzymes. It was established that, except for Indinavir, none of the inhibitors designed against the HIV-1 proteinase were able to inhibit the HTLV-1 proteinase in the studied concentration range, while two reduced peptide bond-containing peptides having the sequence of HTLV-1 cleavage sites were inhibitors of the HTLV-1 proteinase. One of these was potent enough to be used for active site titration of the HTLV-1 proteinase.
Bagossi
Péter
P
Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, H4012 POB 6 Debrecen, Hungary.
Kádas
János
J
Miklóssy
Gabriella
G
Boross
Péter
P
Weber
Irene T
IT
Tözsér
József
J
D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D004796:Clinical Enzyme Tests / Q000379:methods*; D005453:Fluorescence; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019469:Indinavir / Q000494:pharmacology; D007700:Kinetics; D010455:Peptides / Q000378:metabolism; D013379:Substrate Specificity
D010455:Peptides; D019469:Indinavir; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C079711:HTLV-1 protease