Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.7.7 (
DNA polymerase
)
17,007
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
4'-Epiadriamycin
and 4'-O-tetrahydropyranyladriamycin (THP-adriamycin), derivatives of adriamycin, strongly inhibited in vitro reactions of DNA polymerases alpha and beta from calf thymus by competing with activated DNA (template-primer). Preincubation of DNA polymerases with 4'-epiadriamycin or THP-adriamycin strongly inhibited the
DNA polymerase
, but the inhibition was reversed by adding excess amounts of template-primer. These results indicate that 4'-epiadriamycin and THP-adriamycin inhibit the in vitro reactions of DNA polymerases by direct interaction of the drugs with the enzymes as well as by impairing the template activity through intercalation into DNA, in agreement with results obtained for other anthracycline antitumor agents, daunomycin and adriamycin. The activity of
DNA polymerase alpha
may be more sensitive to both 4'-epiadriamycin (Ki, 9 microM) and THP-adriamycin (Ki, 5.5 microM) than that of
DNA polymerase beta
(Ki 30 microM for 4'-epiadriamycin and 22 microM for THP-adriamycin).
DNA polymerase I
from Escherichia coli was inhibited by these drugs in the same manner as
DNA polymerase alpha
. On the other hand, the inhibition of RNA polymerase from E. coli was more marked when the drug was preincubated with template DNA than with the enzyme.
...
PMID:Mechanism of inhibition of DNA polymerases by 4'-epiadriamycin and 4'-O-tetrahydropyranyladriamycin. 636 74
