Adenine formation from guanine

All biosynthetic pathways are under regulatory control by key allosteric enzymes that are influenced by the end products of the pathways. For example, the first step in the pathway for purine biosynthesis is inhibited in a concerted fashion by nucleotides of either adenine or guanine. In addition, the nucleoside monophosphate of each of these bases inhibits its own formation from inosine monophosphate (IMP). On the other hand, adenine nucleotides stimulate the conversion of IMP into GMP, and GTP is needed for AMP formation. 

Ammonium formate was also used in the synthesis of adenine 1 from DAMN [76]. Irrespective of the experimental conditions used for the synthesis of purine nucleobases, only a few procedures for the preparation of guanine have been reported. 

Purine bases are rather less reactive to HOCl than pyrimidines. Thus, in one study, treatment of guanine, adenine, or xanthine (60-62) with 1 or 2 equivalents of HOCl resulted only in high yields of starting material recovery. After prolonged exposure, variable yields of parabanic acid (63) were obtained (Hoyano et al., 1973). This compound has been demonstrated to be formed from both pyrimidines and purines in other high-energy oxidative processes (see, e. g., LeRoux et al. [1969]), but the details of its formation from purines by the HOCl process are not known. 

Figure 25.9 Base pairing of adenine with thymine (a) and cytosine with guanine (b). The dimensions of the thymine-adenine and cytosine-guanine hydrogen-bonded pairs are such that they allow the formation of strong hydrogen bonds and also allow the base pairs to fit inside the two phosphate-ribose chains of the double helix. (Reprinted from Archives of Biochemistry and Biophysics, 65, Pauling, I., Corey,...

It has been recently shown that the selective alkylation and strand scission of deoxytetranucleotide d(GTAG)-27 chosen as DNA model, results from the formation of covalent adducts 28 and 29 on the N-7 of guanine and N-3 of adenine with opening of the cyclopropane ring, respectively. Thermal treatment of 28 (90 °G, 5 min) afforded the d(deoxyribose-TAG) 30 with liberation of N-7 alkyl-guanine 31, while treatment of 29 provided the d(GT-deoxyribose-G) 32 and the N-3 alkyladenine 33 [27]. The stabilities of adducts 28 and 29 were tj/2 = 31 h and 3.2 h, respectively therefore, the cleavage reaction of adduct 29 proceeds much faster than that of 28, Eq. (11) [27]. 

The observation that cisplatin forms adducts with the GpG and ApG (A - adenine p = phosphate) sequences of DNA but not with the GpA sequence has also been probed by molecular mechanics1209,2101. In this case it was found that there is a substantial dependence of the nature of the interactions of one of the ammine ligands from the base on the 3 side (the second in the sequence). When this base is guanine the interaction is a strong hydrogen bond but when it is adenine the interaction is a repulsive interaction between the same amine ligand and the exocyclic -NH2 group of the adenine. This is consistent with formation of the adducts with GpG and ApG and the nonformation of the adduct with GpA. 

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... 

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