ABSTRACT
Isosteric triphosphonate derivatives of 2',3'-dideoxy-2',3'-didehydroadenosine and 3'-deoxy-2',3'-didehydrothymidine and their beta,gamma-substituted analogues were synthesized. Their substrate properties toward a number of reverse transcriptases of the human immunodeficiency and bird myeloblastosis viruses, human DNA polymerases alpha and beta, and the Klenow fragment of Escherichia coli DNA polymerase I were studied.
Subject(s)
Adenosine Monophosphate/analogs & derivatives , DNA-Directed DNA Polymerase/chemistry , Deoxyadenine Nucleotides/chemistry , Dideoxynucleotides/chemistry , Organophosphonates/chemistry , Stavudine/analogs & derivatives , Adenosine Monophosphate/chemistry , Animals , Dideoxynucleotides/chemical synthesis , Humans , Stavudine/chemistry , Substrate SpecificityABSTRACT
The total fraction of aminoacyl-tRNA synthases from Escherichia coli has been shown to catalyze the synthesis of the bis(5'-nucleosidyl) oligophosphates Ap4AZT, Ap4d4T, Ap43TC, and Ap4ACV, as well as Ap3AZT and Ap3d4T, from [alpha-32P]ATP and the corresponding nucleoside-5'-tri(or di)phosphate. The resulting compounds, characterized by HPLC, are resistant to alkaline phosphatase. Ap4AZT, Ap4d4T, and Ap43TC are formed with approximately equal efficiency, whereas the efficiencies of the synthesis of Ap4ACV, Ap3AZT, and Ap3d4T are three- to fivefold lower. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru.
