metabolite of mercaptopurine and thioguanine (TG), deoxythioguanosine triphosphate, was shown to be incorporated into DNA by the polymerase function of.
Deoxythioguanosine triphosphate impairs HIV replication: a new mechanism for an old drug NATALIA F. KRYNETSKAIA,1 JOY Y. FENG,*,1 EUGENE Y. KRYNETSKI, J. VICTOR GARCIA,† JOHN C. PANETTA, KAREN S. ANDERSON,* AND WILLIAM E. EVANS2 St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA; *Yale University School of Medicine, New Haven, Connecticut, USA; and †University of Texas, Southwestern Medical Center, Dallas, Texas, USA Inhibition of HIV-1 reverse transcriptase (RT) and HIV protease are effective mechanisms for anti-retroviral agents, and the combined use of mechanistically different medications has markedly improved the treatment of HIV infected patients. The active metabolite of mercaptopurine and thioguanine (TG), deoxythioguanosine triphosphate, was shown to be incorporated into DNA by the polymerase function of HIV-1 RT and then to abrogate RNA cleavage by HIV-1 RNaseH. Treatment of human lymphocyte cultures with thioguanine produced substantial inhibition of HIV replication (IC50ⴝ0.035 M, IC95ⴝ15.4 M), with minimal toxicity to host lymphocytes (
