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 18.104.22.168) and other retroviral reverse transcriptases, as well as human DNA polymerases α, β, γ (EC 22.214.171.124) and DNA primase (EC 126.96.36.199). 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.
|Original language||English (US)|
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Jun 15 1989|
Bibliographical noteFunding 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.