Desulfurization of 2-thiouracil nucleosides: Conformational studies of 4-pyrimidinone nucleosides

4-Pyrimidinone ribofuranoside (H2o4U) and 4-pyrimidinone 2′-deoxyribofuranoside (dH2o4U) were synthesized by the oxidative desulfurization of parent 2–thiouracil nucleosides with m-chloroperbenzoic acid. The crystal structures of H2o4U and dH2o4U and their conformations in solution were determined and compared with corresponding 2-thiouracil and uracil nucleosides. The absence of a large 2-thiocarbonyl/2-carbonyl group in the nucleobase moiety results in C2′-endo puckering of the ribofuranose ring (S conformer) in the crystal structure of H2o4U, which is not typical of RNA nucleosides. Interestingly, the hydrogen bonding network in the crystals of dH2o4U stabilizes the sugar moiety conformation in the C3′-endo form (N conformer), rarely found in DNA nucleosides. In aqueous solution, dH2o4U reveals a similar population of the C2′-endo conformation (65%) to that of 2′-deoxy-2-thiouridine (62%), while the 62% population of the S conformer for H2o4U is significantly different from that of the parent 2-thiouridine, for which the N conformer is dominant (71%). Such a difference may be of biological importance, as the desulfurization process of natural tRNA 2-thiouridines may occur under conditions of oxidative stress in the cell and may influence the decoding process.

Synthesis, crystal structures and conformations in aqueous solution of 4-pyrimidinone nucleosides were presented.Figure optionsDownload as PowerPoint slide