Guanine basicity

Any one nucleotide, the basic building block of a nucleic acid, is derived from a molecule of phosphoric acid, a molecule of a sugar (either deoxyribose or ribose), and a molecule of one of five nitrogen compounds (bases) cytosine (C), thymine (T), adenine (A), guanine (G), uracil (U). 

It would not be too far fetched to state that life on this planet is totally dependent on two compounds based on the purine nucleus. Two of the bases crucial to the function of DNA and flNA—guanine and adenine—are in fact substituted purines. It is thus paradoxical that the lead for the development of medicinal agents based on this nucleus actually came from observations of the biologic activity of plant alkaloids containing that heterocyclic system, rather than from basic biochemistry. 

Purines — These molecules have basic skeletons of purine heterocycles. Adenine and guanine, intrinsic components of nucleic acids, are also ubiquitous molecules. Related molecules are isoguanine, xanthine, and uric acid. 

In the early days of meteorite analysis, it was difficult to detect N-heterocycles later, the Murchison meteorite was shown to contain xanthine, hypoxanthine, guanine, adenine and uracil (about 1.3 ppm in total). This meteorite seems to contain various classes of basic and neutral N-heterocycles, as well as isomeric alkyl derivatives. 

Reaction of guanine nucleosides and nucleotides with acetaldehyde yields the tricyclic pyrimidopurines (Equation 160), this reaction being accelerated by the addition of a basic amino acid such as arginine or lysine at pH 8 <2002TL6701>. 

In the first family, the metal is coordinated by one molecule of the pterin cofactor, while in the second, it is coordinated to two pterin molecules (both in the guanine dinucleotide form, with the two dinucleotides extending from the active site in opposite directions). Some enzymes also contain FejSj clusters (one or more), which do not seem to be directly linked to the Mo centers. The molybdenum hydroxylases invariably possess redox-active sites in addition to the molybdenum center and are found with two basic types of polypeptide architecture. The enzymes metabolizing quinoline-related compounds, and derivatives of nicotinic acid form a separate groups, in which each of the redox active centers are found in separate subunits. Those enzymes possessing flavin subunits are organized as a2jS2A2, with a pair of 2Fe-2S centers in the (3 subunit, the flavin in the (3 subunit, and the molybdenum in the y subunit. 

The predominant binding site in 9-substituted 6-oxopurines (guanine and hypoxanthine derivatives) is the N7 atom of the base (Figure 6). The prevailing keto tautomer requires proton at N1 even in mildly acidic conditions, which efficiently prevents platination of the N1 site [7]. Under neutral and basic conditions competition of Pt(II) between the N1 and N7 sites has been reported. Attachment of Pt(II) to the N7 atom acidifies the N1H proton and facilitates coordination of additional platinum ions to both N1 and N3 [7]. In N7,N9-blocked 6-oxopurines, the N1 site is the major coordination site [7,24],... 

The bases adenine, guanine, and cytosine all contain exocyclic amino substituents that require protection, since these are potential nucleophiles. They are converted into amides that are stable to the other reagents used in the process, yet can be removed readily by basic hydrolysis. The most effective protecting groups have been found to be isobutyryl for the amino group of guanine, and benzoyl for adenine and cytosine. Thymine has no exocyclic nitrogen and does not need protection. 

Under different basic conditions, glycosylation of guanine derivative 14 was reported to give only triazoline N-3 adduct 15 (Scheme 8) <2001JME4050>. 

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