Guanine reaction with

Cleavage at A or G If the DNA is first treated with acid, dimethyl sulfate methylates adenine at the 3-position as well as guanine at the 7-position (not shown). Subsequent reaction with OH and piperidine triggers degradation and displacement of the methylated A or G purine base and strand scission, essentially as indicated here for reaction of dimethyl sulfate with guanine. 

There are examples in which base radicals undergo reaction with adjacent base residues. The 5-(2 -deoxyuridinyl)methyl radical (63, Scheme 8.30) can forge an intrastrand cross-link with adjacent purine residues. Cross-link formation is favored with a guanine residue on the 5 -side of the pyrimidine radical and occurs under low-oxygen conditions. A mechanism was not proposed for this process, but presumably the reaction involves addition of the nucleobase alkyl radical to the C8-position of the adjacent purine residue. Molecular oxygen likely inhibits crosslink formation by trapping the radical 63, as shown in Scheme 8.24. The radical intermediate 89 must undergo oxidation to yield the final cross-linked product 90,... 

The guanine radical cations (G +) are detected by their reactions with water, which leads after treatment with piperidine or ammonia to selective strand cleavage [14]. A similar charge detection method was used by J.K. Barton, G.B. Schuster and I. Saito as described in their articles in this volume. The cleavage products were separated and quantified by gel electrophoresis. A typical example is shown in Fig. 7 where the GGG unit acts as a thermodynamic sink for the positive charge, and the efficiency of the charge transfer can be measured by the product ratio Pggg/Pg-... 

CT-induced damage, consistent with theoretical predictions that the HOMO of guanine doublets is localized on the 5 -G [90]. Conversely, non-specific oxidation of both guanines is indicative of an alternative chemistry, for instance reaction with singlet oxygen. 

BPDE reacts at several different sites on DNA to generate several kinds of lesions at the N2 (43-45) and N7 (46,47) positions of guanine, apurinic sites (48,49), and strand breaks (50). Which of these lesions are responsible for the transversion mutations at G C sites Evidence derived from a number of experiments suggests the hypothesis that apurinic sites generated by BPDE reactions with DNA are responsible for the transversion mutations ... 

Figure 27.4 Reaction of guanine bases with N-bromosuccinimide causes bromination at the C-8 position of the ring. Amine nucleophiles can be coupled to this active derivative by nucleophilic displacement. Reaction of diamine compounds results in amine-terminal spacers that can be further modified to contain detectable components.

If a DNA adduct involves the nitrogen or oxygen atoms involved in base-pairing, and the adducted DNA is not repaired, base substitution can result. Adducts can be small, such as the simple addition of methyl or ethyl groups, or they can be very bulky, owing to reaction with multiringed structures. The most vulnerable base is guanine, which can form adducts at several of its atoms (e.g., N7, C8, O6 and exocyclic N2) (Venitt and Parry, 1984). Adducts can form links between adjacent bases on the same strand (intrastrand cross-links) and can form interstrand crosslinks between each strand of double-stranded DNA. 

Mercaptopurine is a competitive inhibitor of phosphoribosyl transfer from PRPP to guanine and hypoxanthine, [85a] but does not affect the reaction with... 

Tosylation of 1146 gave 1147, which was converted to the iodo derivative, whose reaction with the sodium salt of guanine, followed by acetylation to aid its purification and then deprotection, gave 1148 (86JMC1384). The hydroxymethyl groups on C-5 of barbituric acid were introduced starting with malonic ester and then reaction with urea (93MI12). 

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