Dinucleoside Phosphates Containing Arabinose or Deoxyxylose. Hydrolysis by Exonucleases and Stacking Properties

Abstract

Abstract Two pairs of isomeric dinucleoside monophosphates containing either 1-β-D-arabinofuranosyl)uracil (arabino-U, aU) or 1-β3-D-2-deoxy-threo-pentofuranosyl) thymine (2′-deoxyxylo-T, dxT) were synthesized. The kinetics of the hydrolysis of these dimers by venom and spleen phosphodiesterases (PDE) were studied. In addition, circular dichroism was used to study their stacking behaviour. A correlation was found to exist between the enzymatic cleavage rate and the conformation of the dimers. It was found that the configuration change at C-2′ or C-3′ in the 5′-terminal nucleoside residue, especially the inversion of 3′-hydroxyl involved into the internucleotide 3′-5′-phosphodiester linkage formation, was critical.