Sequence- and Base-Specific Delivery of Nitric Oxide to Cytidine and 5-Methylcytidine Leading to Efficient Deamination

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• 作者：Md. Monsur Ali ; Md. Rowshon Alam ; Takeshi Kawasaki ; Shizuka Nakayama ; Fumi Nagatsugi ; and Shigeki Sasaki
• 刊名：Journal of the American Chemical Society
• 出版年：2004
• 出版时间：July 28, 2004
• 年：2004
• 卷：126
• 期：29
• 页码：8864 - 8865
• 全文大小：60K
• 年卷期：v.126,no.29(July 28, 2004)
• ISSN：1520-5126

文摘

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.