Guanine, in DNA

Figure 8.2 Base pairing of cytosine or methylcytosine with guanine in DNA. R Phosphodeoxyribose of the DNA backbone.

Guanine is the most easily oxidizable natural nucleic acid base [8] and many oxidants can selectively oxidize guanine in DNA [95]. Here, we focus on the site-selective oxidation of guanine by the carbonate radical anion, COs , one of the important emerging free radicals in biological systems [96]. The mechanism of COs generation in vivo can involve one-electron oxidation of HCOs at the active site of copper-zinc superoxide dismutase [97, 98], and homolysis of the nitrosoperoxycarbonate anion (0N00C02 ) formed by the reaction of peroxynitrite with carbon dioxide [99-102]. 

Mechanism of alkylation of DNA guanine. A bis(chloroethyl)amine forms an ethyleneimonium ion that reacts with a base such as N7 of guanine in DNA, producing an alkylated purine. Alkylation of a second guanine residue, through the illustrated mechanism, results in cross-linking of DNA strands. 

Figure 4.64 Glutathione-mediated activation of 1, 2-dibromoethane. The addition of glutathione is catalyzed by glutathione transferase. Loss of bromide from the glutathione conjugate gives rise to an episulfonium ion. This can react with bases such as guanine in DNA.

Cai Z, Sevilla MD (2000) Electron spin resonance study of electron transfer in DNA inter-double-strand tunneling processes. J PhysChem B 104 6942-6949 Cai Z, Sevilla MD (2003) Electron and hole transfer from DNA base radicals to oxidized products of guanine in DNA. Radiat Res 159 411-419... 

Senthilkumar K, Grozema FC, Guerra CF, Bickelhaupt FM, Siebbeles LDA (2003) Mapping the sites for selective oxidation of guanines in DNA. J Am Chem Soc 125 13658-13659 Setlow B, Setlow P (1993) Binding of small, acid-soluble spore proteins to DNA plays a significant role in the resistance of Bacillus subtilis spores to hydrogen peroxide. Appl Environ Microbiol... 

Example OH adds to guanine in DNA the initial product is an 8-hydroxyguanine radical. 

To investigate the competition between the sulfur atom and the highly reactive GpG sequence we extended this study and used the nucleopeptide model Met-d(TpGpG)-2. Cisplatin is well known to preferentially bind to the N(7) atoms of two neighboring guanines in DNA [81],... 

Building films a layer at a time allowed us to incorporate catalytic metallopolyion catalysts for DNA oxidation into reagentless toxicity biosensors. Two polyions containing Ru(bpy)2+ were used that are capable of cat-alytically oxidizing guanines in DNA. The one shown below, denoted Ru-PVP, has 6 Ru-N bonds and reversible oxidation at 1.15 V vs. SCE. 

Armistead, P.M. Thorp, H.H. Oxidation kinetics of guanine in DNA molecules adsorbed onto ITO electrodes. Anal. Chem. 2001, 73, 558 -564. 

Stemp EDA, Arkin MR, Barton JK. Oxidation of guanine in DNA by Ru(phen)2dppz3+ using the flash-quench technique. J Am Chem Soc 1997 119 2921-5. 

The purine ring system is undoubtedly among the most ubiquitous of all the heterocyclic compounds. This arises not only from the universal occurrence of adenine and guanine in DNA and RNA and of additional modified derivatives in the various tRNAs but also from the subsidiary uses of the ring system in very many biochemical systems Indeed across the whole spectrum of biochemical reactions in living systems there is hardly a reaction sequence which does not involve in some way a purine derivative such as the adenosine or guanosine mono-, di- and tri-phosphates, associated cyclic phosphates and nucleotide coenzymes. 

Figure 27.45. Aflatoxin Reaction. The compound, produced by molds that grow on peanuts, is activated by cytochrome P450 to form a highly reactive species that modifies bases such as guanine in DNA, leading to mutations.

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