4.7 Article

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

Journal

BIOORGANIC & MEDICINAL CHEMISTRY
Volume 19, Issue 7, Pages 2443-2449

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2011.02.008

Keywords

Base modified nucleosides; 4-Pyrimidinone nucleoside; 2 '-Deoxy-2-thiouridine; 2-Thiouridine; Nucleoside conformation; X-ray; NMR

Funding

  1. Technical University of Lodz [DzS I-18/15/2010]
  2. [PBZ-MNiSW-07/I/2007]

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4-Pyrimidinone ribofuranoside (H(2)o(4)U) and 4-pyrimidinone 2 '-deoxyribofuranoside (dH(2)o(4)U) were synthesized by the oxidative desulfurization of parent 2-thiouracil nucleosides with m-chloroperbenzoic acid. The crystal structures of H(2)o(4)U and dH(2)o(4)U 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 H(2)o(4)U, which is not typical of RNA nucleosides. Interestingly, the hydrogen bonding network in the crystals of dH(2)o(4)U stabilizes the sugar moiety conformation in the C3'-endo form (N conformer), rarely found in DNA nucleosides. In aqueous solution, dH(2)o(4)U 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 H(2)o(4)U 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. (C) 2011 Elsevier Ltd. All rights reserved.

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