Zipper-like Watson-Crick base-pairs

A series of DNA heptadecamers containing the DNA analogues of RNA E-like 5' -d(GXA)/(AYG)-5' motifs (X/Y is complementary T/A, A/T, C/G, or G/C pair) w ere studied using nuclear magnetic resonance (NMR) methodology and distance geometry (DG)/molecular dynamics (MD) approaches. Such oligomers reveal ex cellent resolution in NMR spectra and exhibit many unusual nuclear Overhaus er effects (NOEs) that allow for good characterization of an unusual zipper -like conformation with zipper-like Watson-Crick base-pairs; the potential canonical X.Y H-bonding is not present, and the central X/Y pairs are trans formed instead into inter-strand stacks that are bracketed by sheared G-A b asepairs. Such phenomenal structural change is brought about mainly through two backbone torsional angle adjustments, i.e. delta from C2'-endo to CY-e ndo for the sugar puckers of unpaired residues and gamma from gauche(+) to trans for the following 3'-adenosine residues. Such motifs are analogous to the previously studied (GGA)(2) motif presumably present in the human cent romeric (TGGAA)(n) tandem repeat sequence. The novel zipper-like motifs are only 4-7 deg. C less stable than the (GGA)(2) Motif, suggesting that inter -strand base stacking plays an important role in stabilizing unusual nuclei c acid structures. The discovery that canonical Watson-Crick G-C or A-T hyd rogen-bonded pairs can be transformed into stacking pairs greatly increases the repertoire for unusual nucleic acid structural motifs. (C) 2001 Academ ic Press.