Structure of 4'-thioDNA which exhibits endonuclease resistance

Abstract

4'-thio DNA consisting of 2'-deoxy-4'-thionucleosides exhibits resistance to both endonuclease and 3'-exonuclease cleavages. Interestingly, we found that 4'-thioDNA duplex behaved like RNA molecules in hybridization properties and structural aspects. Here, we have determined the structure of 4'-thioDNA duplex in solution by NMR. Most residues take on C3'-endosugar puckering, which is characteristic to A-form. The major groove of 4'-thioDNA duplex is narrow and deep, while the minor groove is wide and shallow. These features are also characteristic to A-form. Thus, although DNA duplex usually takes on B-form in solution, 4'-thioDNA takes on A-form, like RNA molecules. A-form-like groove features of 4'-thioDNA can account for the fact that 4'-thioDNA duplex interacts with an RNA major groove binder, but not with DNA groove binder. Interaction of 4'-thioDNA with RNase V1 and resistance to endonuclease may also be accounted for in the same context.