[Formation of phosphonoester bonds, catalyzed by DNA polymerases].
3'-Fluoro-2',3'-dideoxythymidine 5'-(alpha-methylphosphonyl)-beta, gamma-diphosphate (I) and 2'-deoxythymidine 5'-(alpha-methylphosphonyl)-beta,gamma-diphosphate (II) were synthesised. Reverse transcriptases of HIV and avian myeloblastosis virus, rat liver DNA polymerase beta, calf thymus terminal deoxynucleotidyl transferase and E. coli DNA polymerase I KF incorporated both compounds into the growing DNA chain, KF being the least effective. Compound I revealed termination substrate properties, but II was repeatedly incorporated into the DNA chain, for example, by HIV reverse transcriptase - up to 8 residues. Human placenta DNA polymerases alpha and epsilon incorporated neither I nor II into the DNA chain, although DNA synthesis, catalyzed by all the investigated enzymes, was inhibited in the presence of I or II and compound II was a more effective inhibitor then I. The DNA fragments containing alpha-phosphonomethyl groups were hydrolyzed by 3'----5' exonuclease of DNA polymerase I and not hydrolyzed by ExoIII from E. coli.
Diatkina
N B
NB
Viktorova
L S
LS
Mozaherin
D Iu
DIu
Atrazhev
A M
AM
Rozenberg
S G
SG
Kukhanova
M K
MK
Kraevskiĭ
A A
AA
D000818:Animals; D001345:Autoradiography; D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D001483:Base Sequence; D002384:Catalysis; D002417:Cattle; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D015224:Dideoxynucleosides / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006678:HIV / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D051381:Rats; D013942:Thymine Nucleotides / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D013950:Thymus Gland / Q000201:enzymology
D015224:Dideoxynucleosides; D013942:Thymine Nucleotides; C073273:2'-deoxythymidine-5'-(alpha-methylphosphonyl)-beta,gamma-diphosphate; C073274:3'-fluoro-2',3'-dideoxythymidine-5'-(alpha-methylphosphonyl)-beta,gamma-diphosphate; D012194:RNA-Directed DNA Polymerase; D004259:DNA-Directed DNA Polymerase
Obrazovanie fosfonoéfirnykh sviazeĭ, kataliziruemoe DNK-polimerazami.