Sequence- and base-specific delivery of nitric oxide to cytidine and 5-methylcytidine leading to efficient deamination

Monsur Ali, Rowshon Alam, Takeshi Kawasaki, Shizuka Nakayama, Fumi Nagatsugi, Shigeki Sasaki

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Nitric oxide (NO) is an important endogenous regulatory molecule, and S-nitrosothiols are believed to play a significant role in NO storage, transport, and delivery. On the basis of their ability to generate NO in vivo, S-nitrosothiols can be used as therapeutic drugs. In this study, we have developed an innovative method for sequence- and base-specific delivery of NO to a specific site of DNA followed by specific deamination. We designed a NO transfer reaction from S-nitroso thioguanine to an imino tautomer of cytosine. Nitrosation of the thioguanosine-containing ODN 1 was carried out with S-nitroso-N-acetylpenicillamine (SNAP) to produce ODN 2. An interstrand NO transfer reaction was performed using ODN 2 and its complementary ODN 3 having dC or dmC at the target site, and a rapid NO transfer reaction was observed. In contrast, a transfer reaction was not observed either with ODN 3 having dT, dA, or dG at the target site or with ODN 5-7 having dC at a nontarget site. In the analysis of deaminated products of the NO-transferred ODN 4, it was found that the transformation ratio from dmC to dT was as high as 42% together with the dmC-diazoate (13%). In conclusion, we have demonstrated the innovative method of sequence- and base-specific delivery of nitric oxide to cytidine and 5-methylcytidine. The selectivity and efficiency of NO transfer followed by deamination exhibited in this study are extremely high compared to those of the conventional methods.

Original languageEnglish
Pages (from-to)8864-8865
Number of pages2
JournalJournal of the American Chemical Society
Volume126
Issue number29
DOIs
Publication statusPublished - Jul 28 2004
Externally publishedYes

Fingerprint

Cytidine
Deamination
Nitric oxide
Nitric Oxide
S-Nitrosothiols
5-methylcytidine
Nitrosation
S-Nitroso-N-Acetylpenicillamine
Thioguanine
Cytosine
DNA

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Sequence- and base-specific delivery of nitric oxide to cytidine and 5-methylcytidine leading to efficient deamination. / Ali, Monsur; Alam, Rowshon; Kawasaki, Takeshi; Nakayama, Shizuka; Nagatsugi, Fumi; Sasaki, Shigeki.

In: Journal of the American Chemical Society, Vol. 126, No. 29, 28.07.2004, p. 8864-8865.

Research output: Contribution to journalArticle

Ali, Monsur ; Alam, Rowshon ; Kawasaki, Takeshi ; Nakayama, Shizuka ; Nagatsugi, Fumi ; Sasaki, Shigeki. / Sequence- and base-specific delivery of nitric oxide to cytidine and 5-methylcytidine leading to efficient deamination. In: Journal of the American Chemical Society. 2004 ; Vol. 126, No. 29. pp. 8864-8865.
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