Structures and Stabilities of Small DNA Dumbbells with Watson–Crick and Hoogsteen Base Pairs

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Abstract
The structures and stabilities of cyclic DNA octamers of different sequences have been studied by NMR and CD spectroscopy and by restrained molecular dynamics. At low oligonucleotide concentrations, some of these molecules form stable monomeric structures consisting of a short stem of two base pairs connected by two mini‐loops of two residues. To our knowledge, these dumbbell‐like structures are the smallest observed to date. The relative stabilities of these cyclic dumbbells have been established by studying their melting transitions. Dumbbells made up purely of GC stems are more stable than those consisting purely of AT base pairs. The order of the base pairs closing the loops also has an important effect on the stabilities of these structures. The NMR data indicate that there are significant differences between the solution structures of dumbbells with G–C base pairs in the stem compared to those with A–T base pairs. In the case of dumbbells with G–C base pairs, the residues in the stem form a short segment of a BDNA helix stabilized by two Watson–Crick base pairs. In contrast, in the case of d〈pCATTCATT〉, the stem is formed by two A–T base pairs with the glycosidic angles of the adenine bases in a syn conformation, most probably forming Hoogsteen base pairs. Although the conformations of the loop residues are not very well defined, the thymine residues at the first position of the loop are observed to fold back into the minor groove of the stem.