Pyrimidine, aromaticity nucleotides from

Aromatic compounds arise in several ways. The major mute utilized by autotrophic organisms for synthesis of the aromatic amino acids, quinones, and tocopherols is the shikimate pathway. As outlined here, it starts with the glycolysis intermediate phosphoenolpyruvate (PEP) and erythrose 4-phosphate, a metabolite from the pentose phosphate pathway. Phenylalanine, tyrosine, and tryptophan are not only used for protein synthesis but are converted into a broad range of hormones, chromophores, alkaloids, and structural materials. In plants phenylalanine is deaminated to cinnamate which yields hundreds of secondary products. In another pathway ribose 5-phosphate is converted to pyrimidine and purine nucleotides and also to flavins, folates, molybdopterin, and many other pterin derivatives. 

Purpose. DNA adducts are nucleotide bases (i.e., purines and pyrimidines) that have been covalently modified by reactive electrophilic chemical intermediates or free radicals. The chemical structures of DNA adducts are diverse and vary from simple alkyl adducts induced by alkylating agents to complex bulky adducts such as those resulting from metabolic activation of polycyclic aromatic hydrocarbons, aromatic amines, and aflatoxins (Dipple 1995 Chiarelli and Jackson 1992 Rundle 2006 Xue and Warshawsky 2005). The purpose of measuring DNA adducts is to determine whether a DNA-reactive compound or a metabolically activated... 

Nucleic acids (DNA, RNA) have strong UV absorbances around 260-270 nm arising from n n transitions in the aromatic purine (A, G) and pyrimidine (U, C, T) rings of the nucleotide bases. The sugar phosphate backbone groups absorb only in the far-UV. 

Natural nucleoside bases can be one of five heterocycUc aromatic compounds and include adenine, guanine (the purines), cytosine, thymine and uracil (the pyrimidines). Nucleosides are composed of a base which is attached to a carbohydrate moiety through one of the aromatic ring nitrogen atoms. The specific carbohydrate distinguishes RNA (ribose) from DNA (deoxyribose). Nucleotides are phosphory-lated derivatives of nucleosides and contain one, two, three or (less commonly) four or more phosphate residues either at the 5 position or at the 3 position (Fig. 11.1.1). 

New experiments for the assignment of quarternary carbons in the aromatic rings of nucleotides were described by Furtig et al. The 2D HNC6C5 experiment is derived from the HNCOCA sequence and utilises H1->N1->C6->C5 out-and-back transfer in guanine to correlate HI and C5 resonances. The 2D H8(H6)-C8(C6)-N9(N1)-C4(C2) and Hl -Cr-N9(Nl)-C4(C2) experiments are of HCNC type and correlate HI protons or the aromatic H8/H6 protons with C4 and C2 purines and pyrimidines, respectively. 

Notably, the Dimroth rearrangement has been shown to occur in nature with the purine and pyrimidine bases of nucleosides and nucleotides upon exposure to certain chemical entities. For example, 3,4-epoxybutene, styrene oxide and other aromatic hydrocarbon based epoxides, butadiene and butadiene monoxide, chloroethylene oxirane, chlorambucil, and acrolein, " among others, have been shown to facilitate Dimroth rearrangement, and in some cases subsequent cross-linking of DNA. While interesting from a mechanistic and biological perspective, these reactions will not be reviewed here. 

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