2',3'-Dideoxyadenosine 5'-triphosphate (lithium salt)

2',3'-Dideoxyadenosine 5'-triphosphate (ddATP) is an in vitro inhibitor of reverse transcriptases from retroviruses, including HIV-1 and visna (K_is = 20 and 37 nM, respectively).^1,2,3 It also blocks, in vitro, mammalian and bacterial DNA polymerases.^4,5 ddATP, produced intracellularly by the phosphorylation of exogenously supplied 2',3'-dideoxyadenosine, competes with dATP, resulting in chain termination.^4,5 Because of this activity, dideoxynucleoside 5'-triphosphates, including ddATP, are used to terminate chain extension produced by the Taq polymerase used in polymerase chain reactions.⁶ It is also an antagonist of the purinergic receptor P2X_2/3 (pIC₅₀ = 6.5).⁷

1.Boyle, N.A., Rajwanshi, V.K., Prhavc, M., et al.Synthesis of 2',3'-dideoxynucleoside 5'-α-P-borano-β,γ-(difluoromethylene)triphosphates and their inhibition of HIV-1 reverse transcriptaseJ. Med. Chem.48(7)2695-2700(2005) 2.Frank, K.B., McKernan, P.A., Smith, R.A., et al.Visna virus as an in vitro model for human immunodeficiency virus and inhibition by ribavirin, phosphonoformate, and 2',3'-dideoxynucleosidesAntimicrob. Agents Chemother.31(9)1369-1374(1987) 3.Ueno, T., Shirasaka, T., and Mitsuya, H.Enzymatic characterization of human immunodeficiency virus type 1 reverse transcriptase resistant to multiple 2',3'-dideoxynucleoside 5'-triphosphatesJ. Biol. Chem.270(40)23605-23611(1995) 4.Toji, L., and Cohen, S.S.The enzymatic termination of polydeoxynucleotides by 2',3'-dideoxyadenosine triphosphateProc. Natl. Acad. Sci. USA63(3)871-877(1969) 5.Yagura, T., Kozu, T., and Seno, T.Mouse DNA polymerase accompanied by a novel RNA polymerase activity: Purification and partial characterizationJ. Biochem.91(2)607-618(1982) 6.Li, Y., Mitaxov, V., and Waksman, G.Structure-based design of Taq DNA polymerases with improved properties of dideoxynucleotide incorporationProc. Natl. Acad. Sci. USA96(17)9491-9496(1999) 7.Jarvis, M.F., Bianchi, B., Uchic, J.T., et al.[3H]A-317491, a novel high-affinity non-nucleotide antagonist that specifically labels human P2X2/3 and P2X3 receptorsJ. Pharmacol. Exp. Ther.310(1)407-416(2004)