5-hydroxycytosine

The proton transfer in these clusters via the water bridge was found to be about three times as fast as a nonassisted transfer, underscoring the importance of the solvent for the reaction mechanism [98IJQ855]. In addition to the relative stabilities of the cytosine tautomers, the structures and properties of some cytosine derivatives have been investigated, mainly those of 5-hydroxycytosine 111 and 5,6-dihydroxycytosine 112 (Scheme 73) [99JST1, 99JST49]. 

D Ham, C. Romieu, A. Jaquinod, M. Gasparutto, D. Cadet, J. Excision of 5,6-dihydroxy-5,6-dihydrothymine, 5,6-dihydrothymine, and 5- hydroxycytosine from defined sequence oligonucleotides by Escherichia coli endonuclease III and Fpg proteins Kinetic and mechanistic aspects. Biochemistry 1999, 38, 3335-3344. 

Fig. 8.3. An example of a gas chromatogram of the base-damage to DNA after exposure to hydroxyl radicals (generated radiolytically) - study of the trimethyl-silylated acidic hydrolysate of the modified DNA (modified from Dizdaroglu, 1988 with permission). Peaks I, phosphoric acid II, thymine III and Ilia, cytosine IV and IVa adenine V and Va guanine I uracil 2 5,6-dihydrothymine 3 5-hydroxy-5,6-dihydrothymine 4 5-hydroxyuracil 5 5-hydroxy-5,6-dihydrouracil 6 5-hydroxycytosine 7 cis-thymine glycol 8 /ra .s-thymine glycol 9 5,6-dihydroxyuracil 10 4,6-diamino-5-formamidopyr-imidine 11 8-hydroxyadenine 12 2,6-diamino-4-hydroxy-5-formamidopyrimidine 13...

SCF ab initio calculations of 5-hydroxycytosine predicted that in the vapor phase the oxo-imino isomer is the most stable. However, due to the large difference in the stabilization energy the amino-oxo tautomer is preferred in solution. Increase in the solvent polarity further stabilizes the amino-oxo tautomer (99JST(466)49). The amino-oxo tautomer was also found to be the most stable for 5,6-dihydroxycytosine in solution independent of the solvent polarity (99JST(459)1). 

CGA synthase is specific for UDP-glucuronic acid and for either cytosine or 5-aib-stituted cytosines neither uracil nor adenine were competent acceptors. The relative rates of cytosine derivatives as acceptors in the CGA synthase reaction are given in Tabic 7 (Guo J and Gould SJ, unpublished results). The suitability of 5-fluorocytosine, 10, as a substrate readily explains the production of 5-fluoroblasticidin S, 11, when 10 was fed to S. griseochromogenes (22). The formation of 5-hydroxyCGA from 5-hydroxycytosine (83,84) may be relevant to mildiomycin biosynthesis (85) (see Section HI.D). 

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