Covalent binding of 4-carbamoylbenzenediazonium chloride to deoxyguanine bases of DNA resulting in apparent irreversible inhibition of Poly(adenosine diphosphoribose) polymerase at the nicotinamide binding site
The poly(adenosine diphosphoribose) polymerase activity of isolated liver nuclei was inhibited by 4-carbamoylbenzenediazonium chloride, referred to as 4-diazoniobenzamide, an effect that was dependent on the time of incubation and the concentration of the diazonium compound, with inhibition following first-order kinetics. The inhibition was not reversed by reisolation of nuclie and centrifugal washing, whereas the inhibition by benzamide or 4-aminobenzamide was completely reversible under these conditions. Simultaneous incubation of 4-diazoniobenzamide with benzamide prevented enzyme inhibition. The 4-diazoniobenzoic acid analogue was not inhibitory. The mechanism of action of 4-diazoniobenzamide was traced to a specific covalent binding to (/sup 14/C) dGMP of DNA to form N/sup 2/-((4-carbamoylphenyl)azo)-2'-deoxyguanosine 5'-monophosphate. Coenzymic DNA, by tight association with the polymerase protein, fixes the -C(O)NH/sub 2/ moiety of the adduct at the (/sup 32/P) nicotinamide-binding site of the enzyme.
- Research Organization:
- Univ. of California, San Francisco
- OSTI ID:
- 5639718
- Journal Information:
- Biochemistry; (United States), Vol. 26:8
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DIAZO COMPOUNDS
BIOLOGICAL EFFECTS
POLYMERASES
BIOCHEMICAL REACTION KINETICS
INHIBITION
AMIDES
BENZOIC ACID
CARBON 14 COMPOUNDS
CHEMICAL BONDS
DNA ADDUCTS
ENZYME INHIBITORS
LABELLED COMPOUNDS
LIVER
NICOTINAMIDE
NUCLEAR MAGNETIC RESONANCE
NUCLEOTIDES
PHOSPHORUS 32
TRITIUM COMPOUNDS
ADDUCTS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HETEROCYCLIC COMPOUNDS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAGNETIC RESONANCE
MONOCARBOXYLIC ACIDS
NUCLEI
NUCLEOTIDYLTRANSFERASES
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PYRIDINES
RADIOISOTOPES
REACTION KINETICS
RESONANCE
TRANSFERASES
VITAMIN B GROUP
VITAMINS
550201* - Biochemistry- Tracer Techniques