Thermodynamic effects of formamide on DNA stability

Formamide lowers melting temperature (T-m) of DNAs linearly by 2.4-2.9 degrees C/mole of formamide (C-F) depending on the (G+C) composition, helix conformation and state of hydration, The inherent cooperativity of melting is unaffected by the denaturant, dT(m)/dC(F) for 11 plasmid domains of 0.23 < (G+C) < 0.71 generally fit to a linear dependence on (G+C)-content, which, however, is consistent with a (G+C)-independent alteration in the apparent equilibrium constant for thermally induced helix<->coil transitions, Results indicate that formamide has a destabilizing effect on the helical state, and that sequence-dependent variations in hydration patterns are primarily responsible for small variations in sensitivity to the denaturant, The average unit transition enthalpy <(Delta H)over bar (m)> exhibits a biphasic dependence on formamide concentration, The initial drop of -0.8 kcal/mol bp at low formamide concentrations is attributable to a <delta(Delta H)over bar (m)> for exchange of solvent in the vicinity of the helix: displacement by formamide of weakly bound hydrate or counterion, The phenomenological effects are equivalent to lowering the bulk counterion concentration, Poly(dA . dT) exhibits a much lower sensitivity to formamide, due to the specific pattern of tightly bound, immobilized water bridges that buttress the helix from within the narrow minor groove, Tracts of three (A . T)-pairs behave normally, but tracts of six exhibit the same level of reduced sensitivity as the polymer, suggesting a conformational shift as tracts are elongated beyond some critical length [McCarthy,J.G. and Rich,A, (1991) Nucleic Acids Res. 19, 3421-3429].