Pyrimidine bases, reversible

Reverse transcriptase inhibitors are of two types those that are derivatives of purine- and pyrimidine-based nucleosides and nucleotides (NtRTIs) and those that are not nucleoside or nucleotide based (NNRTIs). 

It is well known that pyrimidine bases convert to photodimers upon irradiation to UV light near the X max( > 270 nm). This photochemical reaction has a lethal effect in biological systems due to the photochemical transformation of pyrimidine bases of nucleic acids. However the photodimerization is a reversible reaction and the photodimers split to afford the original monomers very efficiently upon irradiation at a shorter wavelengths as shown in Scheme 1(1). 

The object of this study is to develop new photoresists for deep-UV lithography, by using the reversible photoreaction of pyrimidine bases (17-19). Applicability of pyrimidine containing polymers to both negative and positive type photoresists is due to this photoreversible reaction in which cyclobutane dimers are either formed or cleaved depending on the exposure wavelength (Scheme 2). 

Just as orotic acid is converted to a ribonucleotide in step e of Fig. 25-14, other free pyrimidine and purine bases can react with PRPP to give monoribonucleotides plus PP . The reversible reactions, which are catalyzed by phosphoribosyltransferases (ribonucleotide pyrophosphorylases), are important components of the salvage pathways by which purine and pyrimidine bases freed by the degradation of nucleic acids are recycled.273 However, thymine is usually not reused. Thymine will react with deoxribose 1-P to form thymidine plus inorganic phosphate (thymidine phosphorylase), and thymidine is rapidly... 

These drugs usually act by inhibiting the polymerases or reverse transcriptases required for nucleic acid synthesis. They are usually analogues of the purine and pyrimidine bases found in the nucleic acids (Figure 7.16). Their general mode of action often involves conversion to the corresponding triphosphate by the host... 

Y. Inaki, Reversible Photoimerization of Pyrimidine Bases, in W. M. Horspool, F. Lenci (Eds.), CRC Handbook of Organic Photochemistry and Photobiology, 2nd Edition, CRC Press, Boca Raton FL, 2004. 

TRANSVERSION MUTATION A base-pair substitution mutation in which the purine pyrimidine base-pair orientation Is reversed, as in adenine thymine - thymine adenine. 

Nucleoside phosphorylases catalyze the reversible phosphorolysis in nucleosides and the transferase reaction involving purine or pyrimidine bases [42]. Scheme... 

Reversed-Phase Ion Pairing of Purine- and Pyrimidine-Based Compounds... 

The specific use of reversed-phase ion-pairing techniques for the simultaneous analysis of purine and pyrimidine bases, nucleosides and, nucleotides has found limited chromatographic application, although it is a technique that warrants further investigation. 

The photobiological activity of the psoralens is related, at least in part, to the ability of these coumarins to undergo [ 2 + 2] photocycloaddition to pyrimidine bases in DNA. The two cis-syn adducts (101) and (102) have now been obtained by irradiation of 2 -deoxycytidine in the presence of 3-carbethoxypsoralen, whereas reversible [ 2 + 2] dimerisation of the coumarin nucleus is preferred on solid state irradiation of the 8-alkoxypsoralen derivative (103). ° [ 2 +, 2] Photoadditions of 7-aminocoumarins... 

Pyrimidine bases are normally salvaged by a two-step route. First, a relatively nonspecific pyrimidine nucleoside phosphorylase converts the pyrimidine bases to their respective nucleosides (Fig. 41.17). Notice that the preferred direction for this reaction is the reverse phosphorylase reaction, in which phosphate is being released and is not being used as a nucleophile to release the pyrimidine base from the nucleoside. The more specific nucleoside kinases then react with the nucleosides, forming nucleotides (Table 41.2). As with purines, further phosphorylation is carried out by increasingly more specific kinases. The nucleoside phosphorylase-nucleoside kinase route for synthesis of pyrimidine nucleoside monophosphates is relatively inefficient for salvage of pyrimidine bases because of the very low concentration of the bases in plasma and tissues. 

RNA and DNA are poly anions at pH 7. The pk of the phosphate OH group is close to 1. DNA is a double helix in which a large purine base is always paired with a small pyrimidine base. Only AT and CG pairs occur. AT and GC pairing are favored by optimal hydrogen bonds, which connect the base pairs in the hydrophobic center (Fig. 8.2.5a). Monomeric AT and GC bases do not pair in water but they do pair in organic solvents. The double helices are destroyed reversibly (they melt ) if the hydrogen bonds are thermally disrupted at temperatures between 70 and 80°C. In UV spectra one then observes a loss of intensity of the bands around 270 nm and a small short-wavelength shift. Each DNA has a characteristic ratio (G+C) (A+T), called the coefficient of specifity, which varies... 

Liquid chromatographic analysis of free purine and pyrimidine bases can be carried out on either cation-exchange or reversed-phase columns. The separation of a mixture of 10 methylated xanthines has been accomplished using reversed-phase LC on a column of Apex Octadenyl 3 pm kept at 50°C, in less than 2 min. This mixture included caffeine, theophylline, and theobromine, which are very important compounds in the food and pharmaceutical industries. 

However, for adenine, guanine, and uracil, the dominant route of anabolism is by way of their ribonucleotide derivatives and traffic along the deoxyribosidic route is not ordinarily significant. Because cytosine is not a substrate for nucleoside phosphorylases, incorporation by the phos-phorylase-kinase route is not possible for this base. The other pyrimidine base of DNA, thymine, is poorly anabolized by both animal and bacterial cells, in spite of the fact that most cells possess thymidine phosphorylase, the action of which is readily reversible. This suggests that ordinarily cellular supplies of deoxyribose 1-phosphate are not available for base anabolism. Experiments are cited below in which it was demonstrated that a significant contribution to the biogenesis of deoxyribose of DNA in E. colt cells did not occur by a route other than ribonucleotide reduction. 

Lochmiiller CH, Hill Jr WB, Porter RM, Hangac HH, Culberson CF, Ryall RR (1983) Separation of Lichen Metabolites, Pyridine Derivatives, and Pyrimidine Bases Using Microbore, Reversed-phase LC. J Chrom Sci 21 70... 

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