Crystal structures of B-DNA with incorporated 2′-deoxy-2′-fluoro-arabino-furanosyl thymines: Implications of conformational preorganization for duplex stability
The fundamental conformational states of right-handed double helical DNA, the A- and B-forms, are associated with distinct puckers of the sugar moieties. The furanose conformation itself is affected by the steric and electronic nature of the ring substituents. For example, a strongly electronegative substituent at the C2′ position, such as in the 2′-deoxy-2′-fluororibofuranosyl analogue, will drive the conformational equilibrium towards the C3′-endo type (north). Conversely, the 2′-deoxy-2′-fluoroarabinofuranosyl modification with opposite stereochemistry at C2′ appears to have a preference for a C2′-endo type pucker (south). Incorporation of 2′-fluoroarabinofuranosyl thymines was previously shown to enhance the thermodynamic stability of B-DNA duplexes. We have determined the crystal structures of the B-DNA dodecamer duplexes [d(CGCGAASSCGCG)]2 and [d(CGCGAASTCGCG)]2 with incorporated 2′-deoxy-2′-fluoroarabinofuranosyl thymines S (south) at 1.55 Å resolution. In the crystal structures, all S residues adopt an O4′-endo conformation (east), well compatible with an overall B-form duplex geometry. In addition to the increased rigidity of S nucleosides, a clathrate-like ordered water structure around the 2′-fluorines may account for the observed larger thermodynamic stability of DNA duplexes containing 2′-deoxy-2′-fluoroarabino thymidine
