title: Sequence- and base-specific delivery of nitric oxide to cytidine and 5-methylcytidine leading to efficient deamination.
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.
authors.affiliation: CREST, Japan Science and Technology Agency, Kawaguchi Center Building, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Md Monsur
authors.initials: MM
authors.lastname: Ali
authors.forename: Md Rowshon
authors.initials: MR
authors.lastname: Alam
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Shizuka
authors.initials: S
authors.lastname: Nakayama
authors.forename: Fumi
authors.initials: F
authors.lastname: Nagatsugi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sasaki
mesh_terms: D003562:Cytidine / Q000031:analogs & derivatives* / Q000737:chemistry*; D003641:Deamination; D009569:Nitric Oxide / Q000737:chemistry*; D020030:Nitric Oxide Donors / Q000737:chemistry*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000737:chemistry; D013379:Substrate Specificity; D013816:Thermodynamics; D013866:Thioguanine / Q000031:analogs & derivatives*
chemical_list: D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D003562:Cytidine; D026423:S-Nitroso-N-Acetylpenicillamine; D013866:Thioguanine; C016568:5-methylcytidine