D-2-Deoxyribose and D-Arabinose, but not D-Ribose, Stabilize the Cytosine Tetrad (i-DNA) Structure

Abstract

Described here are studies exploring the effect of the sugar-phosphate backbone on the stability of i-tetrads in solution [K. Gehring et al. Nature 363, 561–565 (1993)]. In the accompanying paper, branched oligonucleotides are shown to be effective probes for organizing oligodeoxycytidine strands into I-motif structures (C-tetrads). Specifically, the joining of a pair of parallel deoxycytidylate strands with a riboadenosine “linker” leads to marked enhancement in stability of the tetrad structure. To further characterize the nature of the sugar-sugar interactions in this novel structure, branched oligonucleotides containing D-arabinocytidine and D-ribocytidine were synthesized and their association properties examined. The ribo oligomers were prepared in two regioisomeric forms differing only in the connectivities of the deoxycytidine strands, i.e., 3′-to-5′ versus 2′-to-5′ linked dC5 strands. The branched D-deoxycytidine analogue, rA(2′,5′-dC5)3′,5′-dC5, which previously has been shown to fold into a bimolecular I-motif, served as model system. It is found that the arabinose substitution leads to hypochromic structures that are characteristic of four-stranded intercalated DNA and has little, if any, effect on the stability of the complex formed. Parallel experiments with the branched ribocytidine analogs gave very weak or no discernible UV transitions, consistent with no strand association in this case [Lacroix et al., Biochemistry 35, 8715–8722 (1996)]. These results are discussed in relation to expected steric interactions of oligocytidine strands within the I-structure. The findings increase our understanding of the impact of the sugar and intemucleotide connectivity on the stability of this higher-order nucleic acid structure.