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Kinetic analysis of template competitive inhibitors of reverse transcriptases from HIV‐1, MMLV, and AMV

Many viral diseases threaten people's health and there are too few vaccines or viral inhibitors to fight against these viruses. One example is the HIV retrovirus. HIV encodes the enzyme reverse transcriptase (RT) that converts single‐stranded RNA genome of the retrovirus into double‐stranded DNA before the cell begins viral replication. The goal of our research has been to synthesize nucleotide inhibitors that can directly inhibit the activity of RT and prevent viral replication. Four inhibitors molecules synthesized and characterized kinetically are: 1) 2‐S‐(3,4‐dichlorobenzyl)‐etheno‐dATP, 2) 2‐S‐(4‐chlorobenzyl)‐etheno‐dATP, 3) 2‐S‐benzyl‐etheno‐dATP, and 4) 2‐S‐(4‐methoxybenzyl)‐etheno‐dATP. Five component inhibition assays were performed, either as IC50 or Ki plots, against three enzymes, HIV‐1, MMLV, and AMV reverse transcriptases. The results of enzyme assays performed to test the inhibition of HIV RT will be presented.