A two-stranded template-based approach to G center dot(C-A) triad formation: Designing novel structural elements into an existing DNA framework

We have designed a DNA sequence, d(G-G-G-T-T-C-A-G-G), which dimerizes to f orm a 2-fold symmetric G-quadruplex in which G(syn).G(anti).G(syn).G(anti) tetrads are sandwiched between all trans G.(C-A) triads. The NMR-based solu tion structural analysis was greatly aided by monitoring hydrogen bond alig nments across N-H...N and N-H...O=C hydrogen bonds within the triad and tet rad, in a uniformly (C-13,N-15)-labeled sample of the d(G-G-G-T-T-C-A-G-G) sequence. The solution structure establishes that the guanine base-pairs wi th the cytosine through Watson-Crick G.C pair formation and with adenine th rough sheared G-A mismatch formation within the G (C-A) triad. A model of t riad DNA was constructed that contains the experimentally determined G (C-A ) triad alignment as the repeating stacked unit. (C) 2000 Academic Press.