THERMODYNAMICS AND NMR OF INTERNAL GT MISMATCHES IN DNA

Thermodynamics of 39 oligonucleotides with internal G.T mismatches dis solved in I M NaCl were determined from UV absorbance versus temperatu re profiles. These data were combined with literature values of six se quences to derive parameters for 10 linearly independent trimer and te tramer sequences with G.T mismatches and Watson-Crick base pairs. The G.T mismatch parameters predict Delta G(37)(0), Delta H-0, Delta S-0, and T-M with average deviations of 5.1%, 7.5%, 8.0%, and 1.4 degrees C , respectively. These predictions an within the limits of what can be expected for a nearest-neighbor model. The data show that the contribu tion of a single G. T mismatch to helix stability is context dependent and ranges from +1.05 kcal/mol for AGA/TTT to -1.05 kcal/mol for CGC/ GTG. Several tests of the applicability of the nearest-neighbor model to G.T mismatches are described. Analysis of imino proton chemical shi fts show that structural perturbations from the G.T mismatches are hig hly localized. One-dimensional NOE difference spectra demonstrate that G.T mismatches form stable hydrogen-bonded wobble pairs in diverse co ntexts. Refined nearest-neighbor parameters for Watson-Crick base pair s are also presented.