Different patterns of inhibition of avian myeloblastosis virus reverse transcriptase activity by 3'-azido-3'-deoxythymidine 5'-triphosphate and its threo isomer

Publisher Website
Google Scholar
Abstract
The two isomers 3''-azido-3''-deoxythymidine 5''-triphosphate (erythro-AZT-TP) and 1-(3''-azido-2'',3''-dideoxy-.beta.-D-xylofuranosyl)thymine 5''-triphosphate (threo-AZT-TP) were studied as inhibitors of the reverse transcriptase activity of avian myeloblastosis virus. Kinetic analysis of the (rA)n .cntdot. (dT)12-18 (a standard template primer complex of polyriboadenylate and oligodeoxythymidylate of indicated length)-directed reaction revealed that erythro-AZT-TP was a competitive inhibitor with respect to dTTP, whereas threo-AZT-TP was a noncompetitive inhibitor. The apparent Ki values, as calculated from Dixon plots, were 0.48 and 5.5 .mu.M, respectively, compared with a Km value of dTTP of about 70 .mu.M. These results indicate that erythro-AZT-TP had an approximately 150-times-higher affinity to the enzyme than dTTP had and that the avian myeloblastosis virus reverse transcriptase had different binding sites for the two isomers.