Guanines, 8-hydroxy

Deres K, Schroder CH, Paessens A, Goldmann S, Hacker HJ, Weber O, Kramer T, Niewohner U, Pleiss U, Stoltefuss J et al. (2003) Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science 299 893-896 Ehon GB, Furman PA, Fyfe JA, de Miranda P, Beauchamp L, Schaeffer HJ (1977) Selectivity of action of an antiherpetic agent, 9-(2-hydroxy ethoxy methyl) guanine, Proc Natl Acad Sci USA 74 5716-5720... 

Because aromatic purines and purine nucleosides and free purines such as hypo-xanthine and guanine 242 are readily silylated-aminated [64] (cf Scheme 4.24), it is obvious that 6-membered hydroxy-N-heterocycles are analogously silylated-aminated, with reactivity in the order given in Scheme 4.25 [73] X=OTf is the best leaving group and X=NHSiMe3 (cf the transamination as discussed in Section 4.2.4) is the weakest. 

Small quantities of additional purines and pyrimidines occur in DNA and RNAs. Examples include 5-methyl-cytosine of bacterial and human DNA, 5-hydroxy-methylcytosine of bacterial and viral nucleic acids, and mono- and di-N-methylated adenine and guanine of... 

Devasagayam, T.P.A., Steenken, S., Obendorf, M.S.W., Schultz, W.A. and Sies, H. (1991). Formation of 8-hydroxy(deoxy)guanosine and generation of strand breaks at guanine residues in DNA by singlet oxygen. Biochemistry 30, 6283-6289. 

MR Harnden, RL Jarret, MR Boyed, D Sulton, RA Vene Hodge. Prodrugs of the selective antiherpesvirus agent 9-[4-hydroxy-3-(hydroxymethyl) but 1-yl] guanine (BRL 39123) with improved gastrointestinal absorption properties. J Med Chem 32 1738-1743, 1989. 

Some of the following adducts also have been characterized, although not all thoroughly adenosine (108,111). the 0 (87) and N7-guanine derivatives (86-88), phosphate (85) and adducts resulting from the further epoxidation of the 9-hydroxy B[a]P at the 4,5-position (67,68). 

Figure 6. Reaction Mechanism and Formation of Protonated N-Hydroxy Arylamines (VIII). RNH2, N2-guanine- and N8-adenine-nucleic acids ROH, 06-guanine-nucleic acids RCH, C8-guanine- and C8-adenine-nucleic acids.

For neutral guanine two stable tautomers are based on the keto form, labeled guanine I in Figure 5. The remaining three stable structures are based on the hydroxy form, guanine II. In the gas phase, guanine is found in a mixture dominated by the keto forms. In solution, the relative stability of the... 

The amino groups are replaced with oxygen. Although here a biochemical reaction, the same can be achieved under acid-catalysed hydrolytic conditions, and resembles the nucleophilic substitution on pyrimidines (see Section 11.6.1). The first-formed hydroxy derivative would then tautomerize to the carbonyl structure. In the case of guanine, the product is xanthine, whereas adenine leads to hypoxanthine. The latter compound is also converted into xanthine by an oxidizing enzyme, xanthine oxidase. This enzyme also oxidizes xanthine at C-8, giving uric acid. 

Since chemistry of pterines and purines has been already reviewed (42,48,491), only recent studies will be described here. Guanine (93) was prepared by reaction of 4-hydroxy-2,5,6-triaminopyrimidine sulfate (588 see Scheme 73) with HCONH2 with removal of H2O from the reaction system in an excellent yield (492). Also, irradiation of oxygenated aqueous solutions of 6-mercaptopurine with near-UV light gave hypoxanthine (92) as a minor product (< 10%) together with purine-6-sulfinate (589). It also arises from degradation of purine-6-sulfonate obtained from photooxidation of the sulfinate (589) (493). 

Our laboratory conducted the most extensive investigation of the 2,4,1-benzodiazaborines reported to date. We focused attention on l-hydroxy-lff-2,4,l-benzoxazaborine (50a), 1,2-dihydro-l-hydroxy-2,4,l-benzodiazaborine (50b), and 3-amino-l,2-dihydro-l-hydroxy-2,4,l-benzodiazaborine (50c) because their peripheries so closely matched the pyrimidine ring ones of the naturally occurring purines adenine, hypoxanthine, and guanine, respectively <94JA7597>. 

Razskazovskiy et al. employ ESR spectroscopy at low temperatures to investigate electron transfer within brominated DNA [8]. The brominated DNA base electron traps were introduced by bromination of DNA in ice-cooled aqueous solution. The procedure is shown by NMR and GC/MS techniques to modify thymine, cytosine, and guanine, transforming them into 5-bro-mo-6-hydroxy-5,6-dihydrothymine, T(OH)Br, 5-bromocytosine, CBr, and 8-bromoguanine, GBr, derivatives. The bromination products formed in molar ratio close to T(OH)Br/CBr/GBr 0.2 1 0.23 and serve as internal electron scavengers on y-irradiation. Structurally the CBr and GBr are planar, but T(OH)Br is quite nonplanar with the bromine directly above the molecular plane. This disrupts the DNA base stack. Paramagnetic products that result... 

ATP + 9-(4-hydroxy-3-hydroxyniethylbutyl-l-yl)guanine <3> (<3> antiherpesvirus drug penciclovir, recombinant mitochondrial deoxyguanosine kinase, 50% of activity with deoxyguanosine [14]) (Reversibility <3> [14]) [14]... 

Gangcyclovir [9- (l,3-dihydroxy-2-propoxy)methyl guanine 2-amino-l,9- (2-hydroxy-l-hydroxymethyl)-ethoxymethyl -6H-purin-6-one Cytovene Cymeva(e)n(e)] [82410-32-0] M... 

In calf thymus DNA incubated with diepoxybutane, A7-(2 -hydroxy-3, 4 -cpoxybut-l -yl)guanine (Tretyakova et al., 1997b) and V7-(2, 3, 4 -trihydroxybut-l -yl)guaninc (Tretyakova et al., 1996,1997b) [enantiomers not resolved] were formed, as characterized... 

Bolt, H.M. Jelitto, B. (1996) Biological formation of the 1.3-butadiene DNA adducts 7-V-(2-hydroxy-3-buten-l-yl)guanine, 7-V-(l-hydroxy-3-buten-2-yl)guanine and 7-V-(2,3,4-tri-hydroxy-butyl)guanine. Toxicology, 113, 328-330... 

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