Comparison of the effect of Carbovir, AZT, and dideoxynucleoside triphosphates on the activity of human immunodeficiency virus reverse transcriptase and selected human polymerases.
Carbocylic 2',3'-didehydro-2',3'-dideoxyguanosine (Carbovir; NSC 614846) is an antiretroviral agent which may be useful in the treatment of AIDS. We have synthesized the 5'-triphosphate of Carbovir and examined its ability to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (EC 2.7.7.49) and other retroviral reverse transcriptases, as well as human DNA polymerases alpha, beta, gamma (EC 2.7.7.7) and DNA primase (EC 2.7.7.6). Carbovir triphosphate emerges as a highly selective inhibitor of reverse transcriptases with little, if any, effect on the cellular enzymes. 3'-Azido-2',3'-dideoxythymidine (AZT) triphosphate and the two dideoxynucleoside triphosphates, ddTTP and ddGTP, inhibited HIV-1 reverse transcriptase to the same degree as Carbovir triphosphate, but were less selective in that they also inhibited DNA polymerases beta and gamma. We conclude that Carbovir is a highly selective antiretroviral agent.
White
E L
EL
Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, AL 35255.
Parker
W B
WB
Macy
L J
LJ
Shaddix
S C
SC
McCaleb
G
G
Secrist
J A
JA
Vince
R
R
Shannon
W M
WM
D019915:DNA Primase; D003848:Deoxyguanine Nucleotides / Q000494:pharmacology*; D015224:Dideoxynucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D054306:Dideoxynucleotides; D006678:HIV / Q000201:enzymology*; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D012316:RNA Nucleotidyltransferases / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
D003848:Deoxyguanine Nucleotides; D015224:Dideoxynucleosides; D054306:Dideoxynucleotides; D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; C057503:carbovir; D015215:Zidovudine; C031709:2',3'-dideoxyguanosine 5'-triphosphate; D019915:DNA Primase; D012316:RNA Nucleotidyltransferases; C017216:2',3'-dideoxythymidine triphosphate