Evidence for tautornerisrn in nucleic acid base pairs.¹H NMR study of¹⁵N labeled tRNA

Abstract

The imino proton resonances of 15N labeled tRNA appear as asymmetric doublet signals, the asymmetry being dependent on the applied magnetic field strength. Assuming a tautomerism of the type N-H...N not equal to N...H-N in the base pairs the line shapes can be simulated. The most important parameters fitted in the simulation are the rate constants of the proton transfer and the mole fractions of either tautomeric state. The rate constants are of the order of 100s-1 and the mole fractions of the non dominant tautomer about 0.1 depending on the temperature and on the nature of the base pairing. The observations are attributed to a double proton transfer in the base pairs. The unexpectedly slow rates of the double proton transfer process may be connected with a concomitant conformational change of the duplex structure.

Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2′-deoxycytidine

“…natural bases has long been proposed (31)(32)(33)(34)(35), and substantiated in part by experimental evidence of minor tautomeric forms of both canonical bases (36)(37)(38) and certain base analogs (e.g., 5-hydroxy-2′-deoxycytidine) (39). In a search for a chemical rationale to explain the ambiguous pairing of KP1212 during replication, the present study revealed that the compound readily adopts multiple tautomeric forms, some of which were unexpected.…”

“…Multiple tautomeric forms of canonical nucleic acid bases have long been thought to exist and to provide a basis for spontaneous mutations (31)(32)(33)(34)(35)(36)(37)(38). Because minor tautomers (e.g., enol or imino) are typically rare, obtaining direct evidence to support their existence has been a challenge to experimentalists.…”

NMR Study of the Interaction between the lac Repressor and the lac Operator

“…A conformational change, for example to a cruciform structure, should result in a notable loss of intensity as well as in larger shift changes. Although it was difficult to determine whether all the imino protons were still present, no loss in intensity was observed in this reso- Another explanation for the observed shifts could be a change in the equilibrium of the keto-enol tautomers of the bases, recently described for tRNA [42]. Interaction of the D N A bases with protein amino acid residues could result in a stabilisation of the enolic forms, for example by specific hydrogen bonds, thus shifting the equilibrium concentration of the tautomers towards the enolic form.…”

Infrared multiple photon dissociation action spectroscopy of protonated uracil and thiouracils: Effects of thioketo-substitution on gas-phase conformation

“…Specifically, the base-pairing of purine and pyrimidine nucleobases in DNA and RNA requires the correct hydrogen bonding between the nucleobases, cytosine with guanine and adenine with thymine in DNA or uracil in RNA, in order to form stable double helices and correct encoding information [1]. Tautomeric shift of the nucleobases from their canonical tautomers may cause basepairing mismatch and result in mutation [2][3][4][5]. Uracil has been the subject of many experimental [6][7][8][9][10][11][12][13] and theoretical [14][15][16][17][18][19][20][21][22][23][24] studies due to the possibility to form alternative enol tautomers through proton transfer reactions.…”