Carboxyflavins, novel inhibitors of Taq DNA polymerase.
Carboxyflavins were found to be potent selective inhibitors of Taq DNA polymerase in a polymerase chain reaction. The inhibitions were dose-dependent, and complete inhibitions were observed at the concentration of 3.0 microM. Carboxyflavins were much less, or not sensitive to the DNA polymerases tested such as calf thymus DNA polymerase alpha, rat DNA polymerase beta, human immunodeficiency virus type 1 reverse transcriptase, the Klenow Fragment of E. coli DNA polymerase I and T4 DNA polymerase. To our knowledge, there is no other report of an agent that selectively inhibits only a thermophilic polymerase. Interestingly, the carboxyflavins were able to prevent DNA synthesis in the murine lymphoid leukemia cell line L1210 in vitro; almost complete inhibitory levels were achieved in the range of less than 10 microM.
Mizushina
Y
Y
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Ueno
T
T
Goto
Y
Y
Isobe
Y
Y
Sako
M
M
Fujita
T
T
Hirota
K
K
Hayashi
H
H
Sakaguchi
K
K
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004253:DNA Nucleotidylexotransferase / Q000037:antagonists & inhibitors / Q000737:chemistry; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors / Q000737:chemistry; D005415:Flavins / Q000737:chemistry / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry; D015497:HIV-1 / Q000201:enzymology; D007939:Leukemia L1210; D051379:Mice; D051381:Rats; D013045:Species Specificity; D019914:Taq Polymerase / Q000037:antagonists & inhibitors* / Q000737:chemistry
D005415:Flavins; D019914:Taq Polymerase; D004253:DNA Nucleotidylexotransferase; D054303:HIV Reverse Transcriptase; D004256:DNA Polymerase I