Author:
Eriksson B,Vrang L,Bazin H,Chattopadhyaya J,Oberg B
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 myelobastosis virus. Kinetic analysis of the (rA)n X (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 microM, respectively, compared with a Km value for dTTP of about 70 microM. 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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
26 articles.
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1. Theoretical studies of 5-X-2′-deoxyuracils with known antiviral activity. A comparison of molecular mechanics, AM1, and PM3 semiempirical molecular orbital calculations;Journal of Molecular Structure: THEOCHEM;1995-02
2. A Novel Assay System for Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Activity Using a Subclone of a Monocytic Cell Line, U937;Microbiology and Immunology;1994-10
3. Competitive inhibitors of human immunodeficiency virus reverse transcriptase;Perspectives in Drug Discovery and Design;1993-08
4. Synthesis of 2′,3′-Dideoxy-3′-nitro-2′,3′-didehydrothymidine. Its Use as a General Intermediate for the Preparation of Various 2′,3′-Substituted Nucleosides;Nucleosides and Nucleotides;1993-06
5. Structural analysis of 2′,3′-dideoxyinosine, 2′,3′-dideoxyadenosine, 2′,3′-dideoxyguanosine and 2′,3′-dideoxycytidine by 500-MHz 1H-NMR spectroscopy and ab-initio molecul orbital calculations;Journal of Biochemical and Biophysical Methods;1992-01