[Modified nucleoside-5'-triphosphates with an additional conjugated through the 2'-3'-fused ring as DNA polymerase substrates].
5'-Triphosphates of 1-(2',3'-epithio-2',3'-dideoxy-beta-D-lyxofuranosyl) thymine, 1-(2',3'-epithio-2',3'-dideoxy-beta-D-ribofuranosyl) thymine and 2',3'-lyxoanhydrothymidine have been shown to be terminator substrates of human immunodeficiency virus and avian myeloblastosis virus reverse transcriptases as well as DNA polymerase I from E. coli. At the same time they do not terminate DNA synthesis catalysed by DNA polymerase epsilon from human placenta. The KM values of ltTTP, rtTTP and laTTP incorporation into DNA chain agree closely with each other, being 1.5-2.5 times higher than KM for dTTP. Furthermore, Vmax values for modified substrates are only 2-3 times less than Vmax for dTTP. The evidence favours the hypothesis of a great affinity of modified nucleosides with flattened ribose ring of glycone for DNA polymerases active sites.
Semizarov
D G
DG
Viktorova
L S
LS
Kraevskiĭ
A A
AA
Kukhanova
M K
MK
D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D006678:HIV / Q000201:enzymology; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013379:Substrate Specificity
D009711:Nucleotides; D004247:DNA; D012194:RNA-Directed DNA Polymerase; D004256:DNA Polymerase I