DNA and RNA oligomer thermodynamics: The effect of mismatched bases on double-helix stability

The thermodynamic parameters for the double-strand formation of the molecules rCAmG + rCU_nG, m,n = 5–7, and dCA_mG + dCT_nG, m,n = 5,6, were measured from optical melting curves. Normal helices are formed when m = n. The deoxyoligomers are more stable than the ribo-oligomers, due to a more favorable enthalpy. Double helices with mismatched bases can be formed by mixing oligomers with m ≠ n. Such helices may form several possible structures. A structure with a dangling base is favored over a structure with a bulged base. The destabilization of the double strands by the formation of a bulged base was determined to be greater than 1.6 kcal/mol at 10°C. The extent of aggregation in the oligomer double strand rCA₇G·rCU₇G was determined using ultracentrifugation equilibrium. The possible effects of aggregation on the determination of the thermodynamic parameters for double-strand formation are discussed.