Induced-fit recognition of DNA by small circular oligonucleotides.

We have investigated the molecular interaction between cyclic and linear oligonucleotides. We have found that short cyclic oligonucleotides can induce hairpinlike structures in linear DNA fragments. By using NMR and CD spectroscopy we have studied the interaction of the cyclic oligonucleotide d with d, as well as with its two linear analogs d(GTCCCTCA) and d(CTCAGTCC). Here we report the NMR structural study of these complexes. Recognition between these oligonucleotides occurs through formation of four intermolecular Watson-Crick base pairs. The three-dimensional structure is stabilized by two tetrads, formed by facing the minor-groove side of the Watson-Crick base pairs. Overall, the structure is similar to those observed previously in other quadruplexes formed by minor-groove alignment of Watson-Crick base pairs. However, in this case the complexes are heterodimeric and are formed by two different tetrads (G:C:A:T and G:C:G:C). These complexes represent a new model of DNA recognition by small cyclic oligonucleotides, increasing the number of potential applications of these interesting molecules.