[Synthesis of 2',3',-dideoxy-3'-fluoradenosine and -guanosine, their 5'-triphosphates and a study of 2',3'-dideoxy-3'-fluoronucleoside- 5'-triphosphates as substrates for DNA-polymerases].
Potential antiviral and antitumour nucleosides, 3'-fluoro-2', 3'-dideoxy-adenosine and -guanosine, have been synthesized by the chemical transglycosylation reaction using 5'-O-acetyl-3'-fluoro-2', 3'-dideoxy-thymidine and -uridine as donors of the carbohydrate fragment and persilylated 6-N-benzoyladenine and 2-N-palmitoylguanine as acceptors, respectively. 5'-Triphosphates of 3'-fluoro-2', 3'-dideoxy-thymidine, -cytidine, -adenosine, and -guanosine (dNTP(3'F] were synthesized and tested as terminators in cell-free system of DNA synthesis catalyzed by RNA-directed DNA polymerase (reverse transcriptase, RT) from the avian myeloblastosis virus (AMV) and E. coli DNA polymerase I (Klenow fragment). A method of estimating relative effectiveness of dNTP(3'F) incorporation into DNA growing chain in comparison with the natural substrates was developed. It is shown that, in case of AMV-RT, dATP(3'F), dCTP(3'F) incorporate 14 times less efficiently than dATP and dCTP respectively, and dTTP(3'F) 3 times less effectively than the corresponding natural substrates, whereas dGTP (3'F) is as efficient as dGTP. With E. coli DNA polymerase I (Klenow fragment) dATP (3'F) and dCTP(3'F) are ca. 100 times less efficient, and dTTP(3'F) and dGTP(3'F) are ca. 50 times less efficient than the respective natural substrates.
Kvasiuk
E I
EI
Zaĭtseva
H B
HB
Savochkina
L P
LP
Chidzhavadze
Z G
ZG
Bibilashvili
R Sh
RSh
D001483:Base Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D003838:Deoxyadenine Nucleotides / Q000138:chemical synthesis* / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000138:chemical synthesis* / Q000378:metabolism; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D013379:Substrate Specificity
D003838:Deoxyadenine Nucleotides; D003848:Deoxyguanine Nucleotides; D015224:Dideoxynucleosides; C055502:2-fluoro-2',3'-dideoxyadenosine; D016048:Dideoxyadenosine; C055315:3'-fluoro-2',3'-dideoxyguanosine; D004259:DNA-Directed DNA Polymerase
Sintez 2',3'-didezoksi-3'-ftoradenozina i -guanozina, ikh 5'- trifosfatov i izuchenie 2',3'-didezoksi-3'-ftornukleozid-5'-trifosfato v kachestve substratov DNK-polimeraz.