Differential Hydration of dA·dT Base Pairs in Parallel-Stranded DNA Relative to Antiparallel DNA

Parallel-stranded DNA is a novel double-stranded helical form of DNA. Its secondary structure is established by reverse Watson-Crick base pairing between the bases of the complementary strands forming a double helix with equivalent grooves. We have used a combination of magnetic suspension densimetry and isothermal titration calorimetry to obtain complete thermodynamic profiles for the formation of two DNA 25mer duplexes. The duplexes contain exclusively dA·dT base pairs in either parallel (ps-dl·D2) or antiparallel (aps-Dl·D3) orientation. At 15 °C, the formation of each duplex is accompanied by favorable free-energy terms resulting from the partial compensation of favorable exothermic enthalpies and unfavorable entropies and by an uptake of both counterions and water molecules. By taking into account the contribution of single-strand base-stacking interactions and using the formation of the aps-D1·D3 duplex as a reference state to establish a thermodynamic cycle in which the similar single strands cancel out, we obtained a ΔΔG° term of+10 kcal mol⁻¹ duplex formed that results from a partial differential enthalpy-entropy compensation of +32 kcal mol⁻¹ and a ΔΔV of 257 mL mol⁻¹. The positive sign of this enthalpy-entropy compensation together with the marginal differential counterion uptake of 0.2 mol of Na⁺/mol of duplex is characteristic of processes driven by differential hydration and strongly suggests that the parallel duplex is much less hydrated than its antiparallel counterpart by ∼4 mol of water/mol of base pair.