NMR AND MOLECULAR MODELING STUDIES OF 2 PHOTOPRODUCTS OF 2'-DEOXY-4-THIOURIDYLYL-(3',5')-THYMIDINE

Preparation, spectroscopic analysis and molecular modelling of dYo(4-alpha;p)dT and dhs4U(6-alpha;p)dT, two photoproducts of 2'-deoxy-4-thiouridylyl-(3',5')-thymidine are described. The 6(S) configuration of the additional chiral centre of dhs4U(6-alpha;p)dT has been determined using 2D-NMR spectroscopy. NMR data also provided conformational information on the deoxyribose and glycosidic torsion angles of dYo(4-alpha;p)dT and dhs4U(6-alpha;p)dT. The two fragments of dYo(4-a;p)dT have an anti type glycosidic conformation. The furanose conformation of the 5'-end is exclusively C3' -endo and that of -pdT is mainly C2' -endo. A syn/anti glycosidic torsion angle is found for both sugars in dhs4U(6-alpha;p)dT. A C2' -endo/C3' -endo conformation blend exists for the 5' -furanose whereas the second sugar prefers a C2' -endo geometry. The detailed three-dimensional reconstruction of the solution state was performed using NMR guided molecular modelling.