Nitrosative cytosine deamination. An exploration of the chemistry emanating from deamination with pyrimidine ring-opening.

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  • Author(s): Rayat S;Rayat S; Qian M; Glaser R
  • Source:
    Chemical research in toxicology [Chem Res Toxicol] 2005 Aug; Vol. 18 (8), pp. 1211-8.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 8807448 Publication Model: Print Cited Medium: Print ISSN: 0893-228X (Print) Linking ISSN: 0893228X NLM ISO Abbreviation: Chem Res Toxicol Subsets: MEDLINE
    • Publication Information:
      Publication: Washington Dc : American Chemical Society
      Original Publication: Washington, DC : American Chemical Society, c1988-
    • Subject Terms:
      Cytosine/*metabolism ; Nitrogen/*chemistry ; Pyrimidines/*metabolism; Carbamates/chemistry ; Catalysis ; Chromatography, High Pressure Liquid ; Cyclization ; Deamination ; Hydrolysis ; Indicators and Reagents ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Spectrophotometry, Ultraviolet
    • Abstract:
      A discussion of nitrosative deamination of cytosine 1 is presented that argues for the formation of 6 by diazotization of 1 to cytosinediazonium ion 2 and its electrostatic complex 3, dediazoniation to 4 <--> 5, and amide-bond cleavage to 6. The reaction channels available to 6 include hydrolytic deglycation to 3-isocyanatoacrylonitrile 7, water addition to carbamic acid 9 with the possibility for re-closure to uracil 13, water addition to carbamic acid 9, and decarboxylation to 3-aminoacrylonitrile 10. With a view to the instability of the carbamic acid 9, the carbamate models ethyl (Z)-2-cyanovinylcarbamate 14 and (Z)-2-cyano-1-tert-butylvinylcarbamate 20 were studied. Acid-catalyzed hydrolysis of 14 leads to 2-amino-carbonylphenylcarbamate 15, and its cyclization yields the benzo-fused uracil quinazoline-2,4-dione 16. In contrast to the aromatic system 14, acid-catalyzed cyclization cannot compete with oligomerization in the case of 20, and 5-tert-butyluracil 22 is accessible only with base-catalysis. It is shown that 23, the parent of 10, also easily polymerizes. The experimental results provide a rationale as to why 9, 10, and 12 would have escaped detection in in vitro studies: they would have oligomerized. In contrast to the in vitro experiments, the oligomerizations of 9, 10, or 12 clearly are not relevant in vivo because of low monomer concentrations. With the exclusion of recyclization and of oligomerization in vivo, attention thus needs to focus on (Z)-3-aminoacrylonitrile 10 as the most likely deamination product of cytosine aside from uracil.
    • References:
      Proc Natl Acad Sci U S A. 1978 Jan;75(1):233-7. (PMID: 203931)
      Biochemistry. 1990 Mar 13;29(10):2532-7. (PMID: 2185829)
      Biochemistry. 1995 Nov 14;34(45):14752-7. (PMID: 7578083)
      Structure. 1997 May 15;5(5):691-9. (PMID: 9195885)
      Biochemistry. 2005 Mar 1;44(8):2703-15. (PMID: 15723516)
      J Org Chem. 1998 Oct 2;63(20):6867-6877. (PMID: 11672307)
      Antonie Van Leeuwenhoek. 1998 Jul-Oct;74(1-3):89-97. (PMID: 10068792)
      Science. 1991 Nov 15;254(5034):1001-3. (PMID: 1948068)
      Mutat Res. 2001 May 10;485(4):283-307. (PMID: 11585362)
      Mol Microbiol. 1996 May;20(3):467-73. (PMID: 8736526)
      J Org Chem. 2003 Dec 26;68(26):9882-92. (PMID: 14682679)
      Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1574-8. (PMID: 8108447)
      Biochemistry. 1983 Sep 13;22(19):4518-26. (PMID: 6354260)
      J Biol Chem. 1998 May 22;273(21):12689-95. (PMID: 9582291)
      Environ Mol Mutagen. 1988;12(4):431-77. (PMID: 2461302)
      Angew Chem Int Ed Engl. 2003 Jul 7;42(26):2946-74. (PMID: 12851945)
      Environ Mol Mutagen. 2001;37(3):241-83. (PMID: 11317342)
      J Am Chem Soc. 2004 Aug 18;126(32):9960-9. (PMID: 15303870)
      Nature. 1991 Feb 21;349(6311):704-6. (PMID: 1671712)
      Science. 1991 Jul 5;253(5015):49-53. (PMID: 1905840)
      Chem Res Toxicol. 2004 Sep;17(9):1157-69. (PMID: 15377149)
      Biochemistry. 2000 Nov 28;39(47):14611-6. (PMID: 11087417)
      Nat Struct Biol. 1998 May;5(5):347-51. (PMID: 9586994)
      Chem Res Toxicol. 2005 Feb;18(2):111-4. (PMID: 15720113)
      Nature. 1989 Mar 23;338(6213):342-5. (PMID: 2564168)
      N Engl J Med. 1989 Dec 21;321(25):1689-95. (PMID: 2594029)
      J Am Chem Soc. 2004 Mar 3;126(8):2274-5. (PMID: 14982409)
      Chem Pharm Bull (Tokyo). 1985 Aug;33(8):3336-48. (PMID: 4085068)
      Org Lett. 2003 Oct 30;5(22):4077-80. (PMID: 14572253)
      J Am Chem Soc. 2005 Jan 26;127(3):880-7. (PMID: 15656626)
      Mutat Res. 1990 May;238(3):297-304. (PMID: 2188126)
      J Mol Model. 2006 Jul;12(5):731-7. (PMID: 16411080)
      Chem Res Toxicol. 1991 Sep-Oct;4(5):503-9. (PMID: 1665351)
      J Bacteriol. 1975 Feb;121(2):648-55. (PMID: 122971)
      Proc Natl Acad Sci U S A. 1974 Sep;71(9):3649-53. (PMID: 4610583)
      Blood. 1990 Dec 1;76(11):2242-8. (PMID: 1979502)
      Analyst. 2003 Feb;128(2):142-9. (PMID: 12625554)
      Environ Health Prev Med. 2002 Apr;7(1):1-6. (PMID: 21432282)
    • Grant Information:
      R01 GM061027 United States GM NIGMS NIH HHS; R01 GM061027-03 United States GM NIGMS NIH HHS; GM61027 United States GM NIGMS NIH HHS
    • Accession Number:
      0 (Carbamates)
      0 (Indicators and Reagents)
      0 (Pyrimidines)
      8J337D1HZY (Cytosine)
      N762921K75 (Nitrogen)
      O0UC6XOS4H (carbamic acid)
    • Publication Date:
      Date Created: 20050816 Date Completed: 20051209 Latest Revision: 20181113
    • Publication Date:
      20221213
    • Accession Number:
      PMC2546522
    • Accession Number:
      10.1021/tx050082a
    • Accession Number:
      16097794