Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.31.1 (micrococcal nuclease)
 2,818 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The following procedures have been used to prepare fifteen modified dinucleoside monophosphates: (a) bisulfite-catalyzed transamination with aniline to give an N4-phenylcytidine (CPh), (b) bisulfite-catalyzed transamination with beta-naphthylamine to give an N4-beta-naphthylcytidine (CbetaN), (c) alkylation with 7-bromomethylbenz[a] anthracene to afford a 7(benz[a]anthryl-7-methyl)guanosine (GMBA), and (d) reaction with N-acetoxy-2-acetylaminofluorene to give an 8-(N-2-fluorenylacetamido)guanosine (GAAF). The compounds prepared were A-CPh, CPh-A, CPh-G, U-CPh, CPh-U, A-CbetaN, CbetaN-A, G-CbetaN, CbetaN-G, U-CbetaN, CbetaN-U, GMBA-U, U-GMBA, GAAF-U, and U-GAAF. All of the modified compounds were hydrolyzed to the expected monomers with venom and spleen exonucleases. Hydrolysis by micrococcal nuclease was inhibited in the following cases: A-CPh, A-CbetaN, U-GMBA, and U-GAAF. The first three reactions above were applied to denatured calf thymus DNA to prepare modified DNA samples containing from 0.3 to 2.0% bound aromatic residues. The modified nucleic acids were completely hydrolyzed to nucleosides by the combination of venom exonuclease, deoxyribonuclease I and alkaline phosphatase. The same results were obtained with a combination of spleen exonuclease, deoxyribonuclease II, and alkaline phosphatase. Hydrolysis of the modified nucleic acids by micrococcal nuclease and alkaline phosphatase afforded primarily nucleosides, with some dinucleoside monophosphates. The amount of the latter did not exceed that found in the hydrolysis of control DNA, however. Other workers have observed inhibition of enzymatic hydrolysis of nucleic acids modified by aromatic carcinogens. We postulated that their results may have been caused by cross-links, which were avoided in our studies.
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PMID:Preparation and enzymatic hydrolysis of dinucleoside monophosphates and DNA modified with aromatic residues. 55 43

DNA alkylation by four acridine-linked 'DNA-targeted' aniline mustard derivatives has been studied by 32P-postlabelling. P1 nuclease digestion proved much more efficient than butanol extraction for enhancing the yield of adducted bases for these somewhat hydrophilic compounds. The yield of adducts was maximal after approximately 4 h digestion with micrococcal nuclease/spleen phosphodiesterase and remained relatively constant after that up to 24 h, suggesting that the adducts formed are stable under these conditions. There was some variation in the rates of phosphorylation of the adducts by T4 polynucleotide kinase, with optimal labelling generally occurring after 1 h. The (CH2)5O-linked half-mustard derivative 1 gave five nucleotide 3'-diphosphate adduct spots with calf thymus DNA. Two of these were identified as the adenine N1 and N3 adducts, corresponding to those previously identified as the main base adducts formed by 1 following acid digestion studies. The corresponding full mustard also gave five adduct spots. In contrast, the (CH2)3-linked half-mustard 3 gave only two adduct spots, the most intense of which was identified as a guanine adduct. The corresponding full mustard 4 gave three adduct spots, two of which were identified as guanine adducts. These results agree well with those obtained for the same compounds by the more tedious methods of acid digestion to base adducts, followed by isolation on HPLC, and show that the technique of 32P-labelling can be usefully applied to the study of alkylation of DNA by this class of 'targeted' mustards.
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PMID:The use of 32P-postlabelling to detect DNA adducts produced by experimental anticancer drugs: DNA-directed nitrogen mustards. 803 55