Effect of tetramethylammonium ion on the helix-to-coil transition of poly(deoxyadenylylthymidine): a nuclear magnetic resonance and calorimetric investigation.

Differential scanning calorimetry, temperature-dependent NMR, and UV spectroscopy are used to investigate the helix-to-coil transition of poly(deoxyadenylylthymidine) [poly(dA-dT)] in 1 M NaCl and 1 M Me4NCl (tetramethylammonium chloride). All three methods reveal that the polymer has a melting temperature, tm, that is approximately 6 degree C higher in 1 M Me4NCl than in 1 M NaCl. The NMR data show that this increased stability does not result from fundamental changes in base stacking or base pairing in going from 1 M NaCl to 1 M Me4NCl. Consistent with this observation, the calorimetric measurements yield essentially equal enthalpies for the helix-to-coil transition under the two salt conditions (6.8 kcal per base pair in 1 M NaCl and 7.0 kcal per base pair in M Me4NCl). Analysis of the shapes of the calorimetric curves shows that the transition is more cooperative in Me4NCl than in NaCl. Comparison of the calorimetric and van't Hoff enthalpies allows specification of the size of the cooperative unit: 27 base pairs in 1 M NaCl and 32 base pairs in 1 M Me4NCl. The NMR data reveal that the major Me4NCl-induced structural alterations (relative to NaCl) are a change in one glycosidic torison angle and a partial resolution of the two phosphates. The calorimetric experiments indicate that in the absence of fortuitous compensation these conformational changes are not accompanied by a significant enthalpy effect. On the basis of these data, we suggest that in 1 M NaCl poly(dA-dT) assumes predominantly a B-DNA-like conformation where the symmetry repeat occurs every base pair. By contrast, in 1 M Me4NCl the predominant conformation exhibits a dinucleotide repeat consistent with a right-handed alternating B-DNA structure.