Crystal Structure of a Dimethylene Sulfone-Linked Ribodinucleotide Analog

Phosphates, DNA, and the Search for Nonterrean Life: A Second Generation Model for Genetic Molecules

“…Indeed, the G SO 2 C structure (Fig. 3) did so (28). The duplex it formed was remarkably similar to the duplex formed by the natural RNA dimer G PO 2 -C. In both molecules, the crystallographic unit cell contained two molecules in the form of a right-handed double helix with antiparallel orientation of the strands.…”

Primitive Genetic Polymers

“…The results from these studies were intriguing, but less than straightforward to interpret. Although short sulfone-linked DNA analogs (sNAs) were shown to support Watson-Crick base pairing (Roughton et al 1995), longer oligosulfones appeared to have somewhat compromised pairing abilities (Huang et al 1991;Richert et al 1996) and small changes in nucleobase oligosulfone sequence resulted in appreciable changes in oligomer solubility, folding and aggregation Schmidt et al 2003). These authors interpreted the results of these studies as evidence that (1) charged linkages are important for molecular recognition by providing a repulsive energetic term between the two backbones of a duplex, ensuring molecular recognition is largely a function of the nucleobases, (2) that the regular repeating charge limits intramolecular folding of oligomers, thereby allowing these polymers to function well as linear duplexes and as templates for the same during replication, and (3) that, given the dominance of charge in governing the physical properties of these nucleic acids in aqueous solution, changes in DNA/RNA nucleobase sequence have only a second-order effect on polymer properties (i.e., sequence exerts more effect on the molecular recognition of a complementary strand and less effect on helical parameters), thereby allowing the use of virtually any possible nucleotide sequence .…”

Carbohydrate Chemistry for RNA Interference: Synthesis and Properties of RNA Analogues Modified in Sugar-Phosphate Backbone

“…Substitution of a single phosphodiester with the sulfone linkage strongly destabilizes DNA-DNA and DNA-RNA duplexes [82]. Although the crystal structure of dinucleoside analog r(G SO2 C) reveals an only slightly distorted Watson-Crick miniduplex [83], all sulfone-linked octamers do not base pair with complementary oligonucleotides but self-associate and form very stable self-folded structures instead [80,84]. The authors conclude that the absence of the negative charge greatly facilitates formation of the self-structures and that any genetic molecule using Watson-Crick base pairing template must have a charged backbone [85,86].…”