Sheared-type Ganti·Csyn Base-pair: A Unique d(GXC) Loop Closure Motif

Stable DNA loop structures closed by a novel G·C base-pair have been determined for the single-residue d(GXC) loops (X=A, T, G or C) in low-salt solution by high-resolution nuclear magnetic resonance (NMR) techniques. The closing G·C base-pair in these loops is not of the canonical Watson–Crick type, but adopts instead a unique sheared-type (trans Watson–Crick/sugar-edge) pairing, like those occurring in the sheared mismatched G·A or A·C base-pair, to draw the two opposite strands together. The cytidine residue in the closing base-pair is transformed into the rare syn domain to form two H-bonds with the guanine base and to prevent the steric clash between the G 2NH2 and the C H-5 protons. Besides, the sugar pucker of the syn cytidine is still located in the regular C2′-endo domain, unlike the C3′-endo domain adopted for the pyrimidines of the out-of-alternation left-handed Z-DNA structure. The facile formation of the compact d(GXC) loops closed by a unique sheared-type Ganti·Csyn base-pair demonstrates the great potential of the single-stranded d(GXC) triplet repeats to fold into stable hairpins.