Abstract

We have used NMR spectroscopy to study a pyrimidine·purine·pyrimidine DNA triplex containing a non-natural base, 1-(2-deoxy-β-D-ribofuranosyl)- 4-(3-benzamido)phenylimidazole (D 3), in the third strand. The D 3base has been previously shown to specifically recognize T·A and C·G base-pairs viaintercalation on the 3′ side (with respect to the purine strand) of the target base pair, instead of forming sequence-specific hydrogen bonds. 1H resonance assignments have been made for the D 3base and most of the non-loop portion of the triplex. The solution structure of the triplex was calculated using restrained molecular dynamics and complete relaxation matrix refinement. The duplex portion of the triplex has an over-all helical structure that is more similar to B-DNA than to A-DNA. The three aromatic rings of the D 3base stack on the bases of all three strands and mimic a triplet. The conformation of the D 3base and its sequence specificity are discussed.

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