Adenine canonical forms

The DNA lesion 8,5 -cyclo-2 -dG, formed by attack of hydroxyl radicals, contains damage to both base and sugar, and is therefore repaired by nucleotide excision repair enzymes, and is involved in diseases with defective nucleotide excision repair. A mass spectroscopic assay has been developed for the quantitation of the lesion after enzymatic separation of the 5 (R) and 5 (S) isomers. The thermodynamic stability of ODNs containing the oxidative lesion, 2-hydroxy-dA has been examined. It was shown that when the lesion was in the middle of a DNA duplex it behaved as a universal base, in that there was no dilference in Tm when opposite any of the canonical bases. On the other hand, when it was near the termini, there was a preference for base pairing with thymidine, but it also formed base pairs with other nucleotides which was sequence dependent. The extent of oxoprenylation by malondialdehyde or adenine propenal has been investigated in DNA, see (139). ssDNA was found to be more sensitive to oxoprenylation, and supercoiled-DNA more susceptible than linearised plasmid DNA. A variety of intercalators were used, some of which inhibit oxoprenylation, e.g. netropsin, whilst others, like ethidium bromide, caused enhanced oxoprenylation. 

The tautomerism in adenine is displaced towards the canonical amino form both in the gas phase and in solution, and the population of the imino tautomer is too small to play any significant biological role. A different situation occurs for analogs of adenine such as 6-aminopyrazolopyrimidine. The ribo-derivative of this compound (formycin) has very interesting chemotherapeutic properties, and it can be recognized in place of adenine in many biological processes, including incorporation in DNA [110-112]. 

The picture of prototropic trjinsformations of the nucleic acid base tautomers will never be completed without a knowledge of inter- and intramolecular proton transfer kinetics. The most general data describing the kinetics of proton transfer are the set of temperature dependent rate constants. These data for nucleic acid bases are not yet available from either experimental or theoretical studies except the very recent paper [ 134] where the authors attempt to estimate the water assisted proton transfer rate constant for adenine. However, the calculated values of proton transfer barrier for both non-water assisted and water assisted pathways are available for the adenine, guanine and eytosine [119, 123, 134]. These data are collected in Tables 12 - 16, where, for convenience, we have defined as forward reaction the proton transfer process from the normal (canonical) to the hydroxo- (imino-) form. 

Besides the canonical triplexes formed, for example, between thymine and the adenine-thymine base pair and cytosine and the guanine-cytosine base pair other combinations have been suggested to form stable triplexes, e.g. G-TA, G-GC and T-GC [43], The stability of triplexes depends on pH, ionic strength, temperature, and, in cases where the Watson-Crick duplex is part of a plasmid DNA, it depends on supercoil density [44]. 

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