Molecular recognition of Watson-Crick base-pair reversals in triple-helix formation: use of nonnatural oligonucleotide bases.

We report the calculated characteristics of nonnatural triplex-forming oligonucleotide (TFO) bases recognizing base-pair reversals (TA-->AT) in a double-helical DNA sequence. Ab initio and molecular mechanics calculations have been carried out to characterize the geometric and energetic consequences at the base-pair reversal sites. We have estimated the free energies of solvation of the natural and proposed bases by solving the linearized Poisson-Boltzmann equation. The calculations indicate that the proposed TFO bases should bind with some specificity to the duplex. Implications of the strategy used in the context of molecular biology is discussed.