Deoxyguanosine, structure

Experiments on the metabolic activation of 5-MeC in mouse skin are in agreement with the pivotal role of anti-DE-I in expressing its tumorigenicity. The major DNA adduct formed in mouse skin treated with pH]5-MeC has the structure indicated in Figure 5, resulting from addition of the exocyclic amino group of deoxyguanosine to car-... 

Monocrotaline (170) has been the subject of extensive metabolic study with mammalian and microbiological systems. Pyrrolizidine alkaloids such as monocrotaline require metabolic activation to the corresponding pyrrole derivatives or dehydro alkaloids before they are capable of forming covalent bonds with critical macromolecules within the cell. The X-ray structure of dehydromonocrotaline has recently been determined (226), and the ability of dihydroretronicine derived from monocrotaline to react with deoxyguanosine has been demonstrated in vitro (225). 

Aciclovir is a member of a group of nucleoside derivatives termed acyclonucleosides, in that there is an incomplete sugar ring. The structural relationship to 2 -deoxyguanosine should be very clear. Aciclovir is converted into its monophosphate by the viral enzyme thymidine kinase - some viruses also possess enzymes that facilitate their replication in the host cell. The viral enzyme turns out to be much more effective than that of the host cell, and conversion is, therefore, mainly in infected cells. The monophosphate is subsequently converted into the triphosphate hy the host cell enzymes. Aciclovir triphosphate inhibits viral DNA polymerase, much more so than it does the host enzyme, and so terminates DNA replication. 

The purine ring-numbering scheme, 1, and structures of some simple purines, viz. adenine 2, guanine 3, caffeine 4, theophylline 5, adenosine 6, 2 -deoxyadenosine 7, guanosine 8, 2 -deoxyguanosine 9, xanthine 10, and hypoxanthine 11, are shown. 

The structures of the N-substitution products are reminiscent of the C-8 adduct that is the major product of the reaction of 2-fluorenyl-, 4-biphe-nylyl- and other N-arylhydroxylamine and hydroxamic acid esters with 2 -deoxyguanosine, (d-G) 2 deoxyguanosine-5 -phosphate (d-GMP), guano-sine, (G) or DNA in an aqueous environment." The mechanism of this reaction was not seriously investigated for many years because of the mistaken impression that the reaction was inefficient and could not compete with... 

Lomoth R, Naumov S, BredeO (1999) Transients in the oxidation of pyrimidines with SO4 " structure and reactivity of the resulting radicals. J PhysChem A 103 6571-6579 Lu C, Lin W, Wang W, Flan Z, Yao S, Lin N (2000) Riboflavin(VB2) photosensitized oxidation of 2 -deoxyguanosine-5 -monophosphate (dGMP) in aqueous solution a transient intermediates study. Phys Chem Chem Phys 2 329-334... 

Moorthy PN, Hayon E (1975) Free-radical intermediates produced from the one-electron reduction of purine, adenine and guanine derivatives in water. J Am Chem Soc 97 3345-3350 Mori M, Teshima S-l, Yoshimoto H, Fujita S-l, Taniguchi R, Hatta H, Nishimoto S-l (2001) OH Radical reaction of 5-substituted uracils pulse radiolysis and product studies of a common redox-ambivalent radical produced by elimination of the 5-substituents. J Phys Chem B 105 2070-2078 Morin B, Cadet J (1995) Chemical aspects of the benzophenone-photosensitized formation of two lysine - 2 -deoxyguanosine cross-links. J Am Chem Soc 117 12408-12415 Morita H, Kwiatkowski JS,TempczykA(1981) Electronic structures of uracil and its anions. Bull Chem Soc Jpn 54 1797-1801... 

Figure 4 Molecular structures of five DNA nucleosides 2 -deoxyuridine (dU), 2 -de-oxythymidine (dT), 2 -deoxycytidine (dC), 2 -deoxyguanosine (dG), and 2 -deoxyadeno-sine (dA).

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