MECHANISMS OF HUMAN-IMMUNODEFICIENCY-VIRUS RESISTANCE TO AZIDOTHYMIDINE .1. KINETICS OF INTERACTIONS OF REVERSE-TRANSCRIPTASE AND ITS MUTANT FORMS WITH SUBSTRATES AND AZIDOTHYMIDINE 5'-TRIPHOSPHATE

Prolonged therapy of AIDS patients with azidothymidine results in the development of resistance to the drug. This phenomenon was reported to be due to the appearance of point mutations in the structural portion of the gene pol, which encodes for reverse transciptase (RT)(4). Kine tics of interactions of wild and mutant RTs with substrates or azidoth ymidine 5'-triphosphate have been studied. The enzyme was shown to sig nificantly differ from its mutant forms in the affinity for heteropoly mer RNA and DNA templates. The affinity for dNTPs was virtually unaffe cted by the mutations. Their position, however, is significant for the inhibition of reverse transcription with azidothymidine 5'-triphospha te.