THE CRYSTAL-STRUCTURE ANALYSIS OF D(CGCGAASSCGCG)(2), A SYNTHETIC DNADODECAMER DUPLEX CONTAINING 4 4'-THIO-2'-DEOXYTHYMIDINE NUCLEOTIDES

The crystal structure refinement of the synthetic dodecamer d(CGCGAASS CGCG), where S = 4'-thio-2'-deoxythymidine, has converged at R = 0.201 for 2605 reflections with F > 2 sigma(F) in the resolution range 8.0- 2.4 Angstrom for a model consisting of the dodecamer duplex and 66 wat er molecules. A comparison of its structure with that of the native do decamer d(CGCGAATTCGCG) has revealed that the major differences betwee n the two structures is a change in the conformation of the sugar-phos phate backbone in the regions at and adjacent to the positions of the modified nucleosides. Examination of the fine structural parameters fo r each of the structures reveals that the thiosugars adopt a C-3'-exo conformation in d(CGCGAASSCGCG), rather than the approximate C-1'-exo conformation found for the analogous sugars in the structure of d(CGCG AATTCGCG). The observed differences in structure between the two duple xes may help to explain the enhanced resistance to nuclease digestion of synthetic oligonucleotides containing 4'-thio-2'-deoxynucleotides.