Nucleosides tautomeric forms

Fluorescence and phosphorescence emission spectroscopy were employed to study the interaction of E. coli purine nucleoside phosphorylase (PNP) with its specific inhibitor, FA. The results show, for the first time, the application of phosphorescence spectroscopy to the identification of the tautomeric form of the inhibitor bound by the enzyme <2004MI377>. 

Overall NMR and NQR spectroscopy data thus indicate that the diketo structure predominates for uracil, thymine, and their nucleosides or nucleotides. These studies have failed to detect other tautomeric forms of these compounds. 

Tautomeric enol and imino forms of bases occur only rarely, and can lead to mutations. It should be emphasized that in none of the above described mismatch base pairs is there any evidence for the existence of rare tautomeric forms. For the A-C pair, protonation at (adenine)N(l) appears more probable than the imino form (Fig. 20.6). However, conclusive evidence is still lacking because hydrogen atoms cannot be located at the attainable resolution of about 2 A. Moreover, in none of the crystal structures of the nucleosides and nucleotides or of the bases themselves is there any evidence of the enol-imino tautomers (Part II, Chaps. 15, 16, 17). 

NMR studies on purine nucleosides have been undertaken to assign the site of glycosylation, to determine the anomeric Configuration, to elucidate the sugar puckering and to determine the synjanti ratio of the location of the bases. Rare tautomeric forms and protonation sites were also studied. 

Among the species produced upon radiolysis of water, hydroxyl radical ( OH) is the most reactive. Indeed, its reaction rate with the four bases and related nucleosides is diffusion-controlled. The main reactive sites of hydroxyl radicals on nucleobases are the double-bonds of the heterocycles. Accordingly, addition of OH at the C8 position of adenine and guanine yields the corresponding reducing 8-hydroxy-7,8-dihydropurin-7-yl radical (Fig. 2). Oxidation of this intermediate leads to the formation of related 8-hydroxypurines that are in dynamic equilibrium with their more stable 8-oxo-7,8-dihydropurine tautomeric form. Competitive reduction of the latter purine radical gives rise to imidazole ring opened compounds the... 

The non-natural pyrid[2,3-d] pyrimidine nucleoside (195) pairs preferentially with guanine and adenine in DNA but specifically recognises AT base pairs within the triple helix structure. It is thought that this sequence specificity may be caused by the ability of the nucleoside to adopt different tautomeric forms. 

Infrared spectra of heavy-water solutions have been used to determine the tautomeric forms of nucleosides, nucleotides, and polynucleotides and to study the... 

The heterocyclic bases obtained from nucleosides are capable of existing in more than one tautomeric form. The forms that we have shown are the predominant forms that the bases assume when they are present in nucleic acids. 

Uracil reacts with hydrazine to give pyrazol-3(2if)-one (944) and urea N-methyl- and dimethyl-hydrazine behave similarly to give the 2-methyl- and 1,2-dimethyl derivatives. The reactions of hydrazines with uridine and related nucleosides and nucleotides is well studied (67JCS(C)1528). The tautomerism and predominant form of uracil are discussed in Section 2.13.1.8.4. 

The optical properties of the 8-o-PhOH-purine adducts have provided insight into their ground-state structures at the nucleoside level. These adducts have the ability to phototautomerize, through an excited-state intramolecular proton transfer (ESIPT) process, to generate the keto form. This tautomerization depends on the presence of a intramolecular hydrogen (H)-bond between the phenolic OH and the imine nitrogen (N-7). Figure 14 shows normalized absorption and emission spectra for 8-o-PhOH-dG and 8-o-PhOH-dA in aqueous buffered water and hexane. In water, 8-o-PhOH-dG shows only enol emission at 395 nm, while 8-o-PhOH-dA shows enol emission at 374 nm and phenolate emission at 447 nm. In hexane, both adducts show keto emission at 475 nm 8-o-PhOH-dA also shows a small amount of enol emission and no phenolate emission. These results show that in water, the intramolecular H-bond... 

The nucleoside formed from hypoxanthine and ribose is known as inosine (Ino or I) and the corresponding nucleotide as inosinic acid. Further substitution at C-2 of -H by -OH and tautomerization yields xanthine (Xan). Its nucleoside is xanthosine (Xao, X). A similar hydroxylation at C-7 converts xanthine to uric acid, an important human urinary excretion product derived from nucleic acid bases. 

Nucleoside analogues do not always behave as expected. 5-Bromouracil (6.a) effectively forms base pairs with guanine nucleotides. This surprising observation has been explained by invoking a different tautomer of 6.a. Draw a different tautomer of 6.a and show how it can effectively base pair to a guanine nucleotide. (Tautomerization theory Topal, M. D., Fresco, J. R. Base Pairing and... 

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