Calorimetric study of 2U:1A three‐stranded complexes formed between poly(U) and adenine dinucleotides: ApA and diastereoisomers of nonionic adenine dideoxyribonucleoside methyl phosphonate

Melting parameters of 2U:1A complexes formed by polyuridylic acid [poly(U)] and three adenine dinucleotides, diribonucleoside monophosphonate ApA and diastereoisomers of dideoxyribonucleoside methyl phosphonate [(dApA)1 and (dApA)2], in 1M NaCl and at a number of dinucleotide concentrations were obtained from differential scanning microcalorimetric data and interpreted in terms of the theory of helix–coil equilibrium in oligonucleotide–polynucleotide systems. The apparent binding constant, 1/cm, at 39°C and melting temperatures, Tm, at 1 × 10−3 M dinucleotide concentration indicate the following order of thermodynamic stability of the complexes: 2 poly(U) · (dApA)2 (2.27 × 103M−1, 44.2°C) > 2 poly(U) · (dApA)1 (9.9 × 102M1, 39.2°C) > 2 poly(U) · (ApA) (5.9 × 102M−1, 35.8°C). Corresponding calorimetric enthalpies of melting, ΔHm: 13.5, 12.7, and 12.8 kcal/mol (UUA base triplets) were found to be considerably lower than the van't Hoff enthalpies, ΔHapp: 29.4, 16.2, and 16.2 kcal/mol, respectively, evaluated from the dependence of the melting temperatures on dinucleotide concentration. Self‐association of dinucleotides and their simultaneous binding as monomers, dimers, and higher‐order associated species is suggested as the most probable cause of the differences between ΔHm and ΔHapp values. The differences in thermodynamic properties of the complexes formed by (dApA)1 and (dApA)2 diastereoisomers are discussed in connection with their known conformational properties. The higher and essentially enthalpic stability of the 2 poly(U) · (dApA)2 complex correlates with a lower degree of intramolecular stacking of the (dApA)2 isomer. The hydrophobically enhanced strong self‐association of the latter greatly influences the thermodynamics of its complex formation with poly(U) and results in ΔHapp/ΔHm = 2.3.