Crystal and molecular structures of carbon-bridged pyrimidine cyclonucleosides. Substrate analogs of ribonuclease A

The crystal and molecular structures of carbon-bridged 6,5'-cyclo-5'-deoxy-4-thiouridine (6,5'-Cs4U), 6,5'-cyclo-5'-deoxy-2',3'-O-isopropylideneuridine (6,5'-CiU) and 6,6'-cyclo-5',6'-dideoxy-allofuranosyluracil (6,6'-CU) have been determined by X-ray diffraction. The molecular conformations of 6,5'-Cs4U and 6,5'-CiU are very similar; the conformation about the glycosidic bond is anti (low region), the torsion angle O(4')-C(1')-N(1)-C(2) being -150.0 degrees for 6,5'-Cs4U and -145.5 degrees for 6,5'-CiU, and the sugar puckering being both O(4')-exo. On the other hand, 6,6'-CU takes the glycosidic torsion angle of -116.9(4) degrees (middle anti region) and the sugar conformation of C(4')-endo. The cyclization causes little alteration in the geometry of the base moiety. 6,5'-Cs4U and 6,5'-CiU exhibit the similar base-base interactions between adjacent molecules, although their molecular packings are quite different; the 4-thiouracil or uracil moiety interacts with adjacent base moieties through hydrogen bonding and stacking interactions. In 6,6'-CU, cyclonucleosides were connected by hydrogen bondings between the hydroxyl and sugar ring oxygen atoms and between the hydroxyl groups and the base nitrogen and oxygen atoms. As the 2',3'-cyclic phosphates of these carbon-bridged cyclonucleosides are hydrolyzed by ribonuclease A, it is suggested that the conformers found in these cyclonucleosides are recognized by the enzyme.