TY - JOUR
T1 - Comparison of the effect of Carbovir, AZT, and dideoxynucleoside triphosphates on the activity of human immunodeficiency virus reverse transcriptase and selected human polymerases
AU - White, E. Lucile
AU - Parker, William B.
AU - Macy, Lisa J.
AU - Shaddix, Sue C.
AU - McCaleb, George
AU - Secrist, John A.
AU - Vince, Robert
AU - Shannon, William M.
N1 - Funding Information:
Acknowledgments: This work was funded in part by NIH Grant ROl CA23263 and a grant from the University of Minnesota. Discussions with A. T. Shortnacy about the synthesis of Carbovir-TP and with L. Lee Bennett, Jr. regarding the enzyme inhibition studies are gratefully acknowledged.
PY - 1989/6/15
Y1 - 1989/6/15
N2 - 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 α, β, γ (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 β and γ. We conclude that Carbovir is a highly selective antiretroviral agent.
AB - 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 α, β, γ (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 β and γ. We conclude that Carbovir is a highly selective antiretroviral agent.
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U2 - 10.1016/0006-291X(89)92611-9
DO - 10.1016/0006-291X(89)92611-9
M3 - Article
C2 - 2472136
AN - SCOPUS:0024354118
SN - 0006-291X
VL - 161
SP - 393
EP - 398
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
