Thermodynamic effects of formamide on DNA stability

Nucleic Acids Res. 1996 Jun 1;24(11):2095-103. doi: 10.1093/nar/24.11.2095.


Formamide lowers melting temperatures (Tm) 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. dTm/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(m)[see text for complete expression], 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(m)[see text for complete expression], 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].

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Composition
  • Base Sequence
  • DNA / chemistry*
  • DNA / drug effects*
  • Drug Stability
  • Formamides / pharmacology*
  • Hot Temperature
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Plasmids
  • Poly dA-dT / chemistry
  • Thermodynamics


  • Formamides
  • Poly dA-dT
  • formamide
  • DNA