Analysis of interactions of DNA polymerase beta and reverse transcriptases of human immunodeficiency and mouse leukemia viruses with dNTP analogs containing a modified sugar residue.
Substrate properties of various morpholinonucleoside triphosphates in the reaction of DNA elongation catalyzed by DNA polymerase beta, reverse transcriptase of human immunodeficiency virus (HIV-1 RT), and reverse transcriptase of Moloney murine leukemia virus (M-MuLV RT) were compared. Morpholinonucleoside triphosphates were utilized by DNA polymerase beta and HIV-1 reverse transcriptase as substrates, which terminated further synthesis of DNA, but were virtually not utilized by M-MuLV reverse transcriptase. The kinetic parameters of morpholinoderivatives of cytosine (MorC) and uridine (MorU) were determined in the reaction of primer elongation catalyzed by DNA polymerase beta and HIV-1 reverse transcriptase. MorC was a more effective substrate of HIV-1 reverse transcriptase and significantly less effective substrate of DNA polymerase beta than MorU. The possible use of morpholinonucleoside triphosphates as selective inhibitors of HIV-1 reverse transcriptase is discussed.
Lebedeva
N A
NA
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
Seredina
T A
TA
Silnikov
V N
VN
Abramova
T V
TV
Levina
A S
AS
Khodyreva
S N
SN
Rechkunova
N I
NI
Lavrik
O I
OI
D002384:Catalysis; D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis; D003854:Deoxyribonucleotides / Q000378:metabolism / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology; D007700:Kinetics; D008979:Moloney murine leukemia virus / Q000201:enzymology; D009025:Morpholines / Q000378:metabolism / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004279:DNA, Viral; D003854:Deoxyribonucleotides; D009025:Morpholines; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D019951:DNA Polymerase beta