Purine rings

Table 28 2 doesn t include all of the nucleoside components of nucleic acids The presence of methyl groups on pyrimidine and purine rings is a common and often important variation on the general theme... 

FIGURE 11.2 (a) The pyrimidine ring system by convention, atoms are numbered as indicated, (b) The purine ring system, atoms numbered as shown. 

The aromaticity of the pyrimidine and purine ring systems and the electron-rich nature of their —OH and —NHg substituents endow them with the capacity to undergo keto-enol tautomeric shifts. That is, pyrimidines and purines exist as tautomeric pairs, as shown in Figure 11.6 for uracil. The keto tautomer is called a lactam, whereas the enol form is a lactim. The lactam form vastly predominates at neutral pH. In other words, pA) values for ring nitrogen atoms 1 and 3 in uracil are greater than 8 (the pAl, value for N-3 is 9.5) (Table 11.1). 

The 8-aza analogs are formally derived by substitution of the methine group in position 8 of the purine ring. The names thus derived preserve the numbering of the purine ring (146), and are frequently used in papers of biochemical character, but in chemical papers only along with systematic names. 

Anti-gout Drugs. Figure 1 Xanthine oxidase-catalyzed reactions. Xanthine oxidase converts hypoxanthine to xanthine and xanthine to uric acid, respectively. Hypoxanthine and xanthine are more soluble than uric acid. Xanthine oxidase also converts the uricostatic drug allopurinol to alloxanthine. Allopurinol and hypoxanthine are isomers that differ from each other in the substitution of positions 7 and 8 of the purine ring system. Although allopurinol is converted to alloxanthine by xanthine oxidase, allopurinol is also a xanthine oxidase inhibitor. Specifically, at low concentrations, allopurinol acts as a competitive inhibitor, and at high concentrations it acts as a noncompetitive inhibitor. Alloxanthine is a noncompetitive xanthine oxidase inhibitor. XOD xanthine oxidase. 

The reaction temperature varies between -40 and 110 °C, depending on the reactivity of both counterparts, amine and chlorophosphane. As usual, aliphatic amino groups react faster than aromatic and heteroaromatic ones due to their greater nucleophilic strength. These differences in reactivity allow chemose-lective phosphinous amide formation, as that represented in Scheme 2 where the P-N bond is formed exclusively at the aliphatic NH2 group of 2 but not at the heteroaromatic NH2, whose lone pair is extensively delocalized in the electron-withdrawing purine ring [35]. 

Figure 34-1. Sources of the nitrogen and carbon atoms of the purine ring. Atoms 4,5, and 7 (shaded) derive from glycine.

Nucleobases, including 9-methyl-, 9-ethyl-, 1,9-dimethyl-guanine and 2-amino-6-methoxy-9-methylpurine, form complexes of the type Au(N)Cl3 when reacted with [AuCU] in water at pH 3—4. Binding of a AuCh unit to the N (7) position of the purine ring was confirmed by X-ray crystallography [26]. 

Much research has centered on identifying the source of the purine ring in caffeine. Two possible sources are likely methylated nucleotides in the nucleotide pool and methylated nucleotides in nucleic acids. Extensive experimental work by Suzuki and Takahashi27-30 proposes a scheme whereby caffeine is synthesized from methylated purines in the nucleotide pool via 7-methylxanthosine and theobromine. Information relating to the formation of 7-methylxanthine from nucleotides in the nucleotide pool is sparse. They also provide data that demonstrate that theophylline is synthesized from 1-methyladenylic acid through 1-methylxanthine as postulated by Ogutuga and Northcote.31... 

P2j Z = 2 D = 1.57 R = 0.048 for 931 intensities. The base exists in the thioxo form, with C-8=S and N-7 protonated. The 8-thio substituent causes the base to assume the syn (—102.6°) orientation. The o-ribosyl group is 2T3 (174.8 °, 44.1 °). The exocyclic, C-4 -C-5 bond orientation is trans (—173.2°). This does not favor intramolecular hydrogen-bonding of 0-5 to N-3 of the syn base. The C=S distance is 166.8 pm. The S atom is involved in a weak, acceptor hydrogen-bond to a water molecule, S H-O(w) = 361 pm. The bases are stacked head-to-tail, with overlap of the C=S bonds and the purine ring, in contrast to the known, related structure l-/ -D-ribofuranosyl-2-thioxo-3ff-benzimidazole,197 where similar head-to-tail stacking of the bases involves overlap of the base rings only. 

Hypermodified nucleosides that contain an attached amino acid at C(6) are important in the biochemistry of RNAs. The Ni11 complex with N-[(9-/3-D-ribofuranozylpurin-6-yl)-carbamoyl]-threonine (699) forms a very stable complex involving N(l) of the purine ring, the amide-N and the carboxylate of the attached threonine as donors.1837... 

Figure 1.38 The pyrimidine and purine ring structures common to nucleic acids.

The major difference between purine and pyrimidine de novo biosynthesis is that the pyrimidine ring is assembled and then added to PRPP (Fig. 20-1). With purines, the purine ring is built directly on the PRPP. 

Before the advent of enediyne antitumor antibiotics, there had been few examples of carbon radicals believed to mediate DNA cleavage. The simplest of all, the methyl radical has been shown to effect DNA cleavage under enzymatic as well as chemical conditions [24]. Oxidation of methylhydrazine by horseradish peroxidase or ferricyanide (Fig. 5) gave high yields of methyl radicals, which were shown to cleave DNA by purine ring alkylation. 

Upon purification of the XDH from C. purinolyticum, a separate Se-labeled peak appeared eluting from a DEAE sepharose column. This second peak also appeared to contain a flavin based on UV-visible spectrum. This peak did not use xanthine as a substrate for the reduction of artificial electron acceptors (2,6 dichlor-oindophenol, DCIP), and based on this altered specificity this fraction was further studied. Subsequent purification and analysis showed the enzyme complex consisted of four subunits, and contained molybdenum, iron selenium, and FAD. The most unique property of this enzyme lies in its substrate specificity. Purine, hypoxanthine (6-OH purine), and 2-OH purine were all found to serve as reductants in the presence of DCIP, yet xanthine was not a substrate at any concentration tested. The enzyme was named purine hydroxylase to differentiate it from similar enzymes that use xanthine as a substrate. To date, this is the only enzyme in the molybdenum hydroxylase family (including aldehyde oxidoreductases) that does not hydroxylate the 8-position of the purine ring. This unique substrate specificity, coupled with the studies of Andreesen on purine fermentation pathways, suggests that xanthine is the key intermediate that is broken down in a selenium-dependent purine fermentation pathway. ... 

Barriers to rotation about the exocyclic C—N bonds, due to resonance interactions with the purine rings, have recently been calculated by the CNDO/2 method for all the nucleotide bases (cytosine, adenine, guanine) (Rao and Rao, 1973). 

Table 2.2. SUBSTRATE SPECIFICITY OF ADENOSINE KINASE A. Variation of substituents on purine ring... 

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