D-2-DEOXYRIBOSE AND D-ARABINOSE, BUT NOT D-RIBOSE, STABILIZE THE CYTOSINE TETRAD (I-DNA) STRUCTURE

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 olig onucleotides are shown to be effective probes for organizing oligodeox ycytidine strands into I-motif structures (C-tetrads). Specifically, t he joining of a pair of parallel deoxycytidylate strands with a riboad enosine ''linker'' leads to marked enhancement in stability of the tet rad structure. To further characterize the nature of the sugar-sugar i nteractions in this novel structure, branched oligonucleotides contain ing D-arabinocytidine and D-ribocytidine were synthesized and their as sociation properties examined. The ribo oligomers were prepared in two regioisomeric forms differing only in the connectivities of the deoxy cytidine strands, i.e., 3'-to-5' versus 2'-to-5' linked dC(5) strands. The branched D-deoxycytidine analogue, rA(2',5'-dC(5))3',5'-dC(5), wh ich previously has been shown to fold into a bimolecular I-motif, serv ed as model system. It is found that the arabinose substitution leads to hypochromic structures that are characteristic of four-stranded int ercalated DNA and has little, if any, effect on the stability of the c omplex formed. Parallel experiments with the branched ribocytidine ana logs gave very weak or no discernible UV transitions, consistent with no strand association in this case [Lacroix et al., Biochemistry 35, 8 715-8722 (1996)]. These results are discussed in relation to expected steric interactions of oligocytidine strands within the I-structure. T he findings increase our understanding of the impact of the sugar and internucleotide connectivity on the stability of this higher-order nuc leic acid structure.