Sequence- and base-specific delivery of nitric oxide to cytidine and 5-methylcytidine leading to efficient deamination.
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.
Ali
Md Monsur
MM
CREST, Japan Science and Technology Agency, Kawaguchi Center Building, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
Alam
Md Rowshon
MR
Kawasaki
Takeshi
T
Nakayama
Shizuka
S
Nagatsugi
Fumi
F
Sasaki
Shigeki
S
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*
D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D003562:Cytidine; D026423:S-Nitroso-N-Acetylpenicillamine; D013866:Thioguanine; C016568:5-methylcytidine