Comparison of the thermodynamics and base-pair dynamics of a full LNA:DNA duplex and of the isosequential DNA:DNA duplex

Locked nucleic acids (LNA), conformationally restricted nucleotide analogues, are known to enhance pairing stability and selectivity toward complementary strands. With the aim to contribute to a better understanding of the origin of these effects, the structure, thermal stability, hybridization thermodynamics, and base-pair dynamics of a full-LNA:DNA heteroduplex and of its isosequential DNA:DNA homoduplex were monitored and compared. CD measurements highlight differences in the duplex structures: the homoduplex and heteroduplex present B-type and A-type helical conformations, respectively. The pairing of the hybrid duplex is characterized, at all temperatures monitored (between 15 and 37 degrees C), by a larger stability constant but a less favorable enthalpic term. A major contribution to this thermodynamic profile emanates from the presence of a hairpin structure in the LNA single strand which contributes favorably to the entropy of interaction but leads to an enthalpy penalty upon duplex formation. The base-pair opening dynamics of both systems was monitored by NMR spectroscopy via imino protons exchange measurements. The measurements highlight that hybrid G-C base-pairs present a longer base-pair lifetime and higher stability than natural G-C base-pairs, but that an LNA substitution in an A-T base-pair does not have a favorable effect on the stability. The thermodynamic and dynamic data confirm a more favorable stacking of the bases in the hybrid duplex. This study emphasizes the complementarities between dynamic and thermodynamical studies for the elucidation of the relevant factors in binding events.

Stability Problems in Inverse Diffraction

Inverse diffraction consists in determining the field distribution on a boundary surface from the knowledge of the distribution on a surface situated within the domain where the wave propagates. This problem is a good example for illustrating the use of least-squares methods (also called regularization methods) for solving linear ill-posed inverse problem. We focus on obtaining error bounds For regularized solutions and show that the stability of the restored field far from the boundary surface is quite satisfactory: the error is proportional to ∊(ðŗ‚ ≃ 1) ,ðŗœ being the error in the data (Hölder continuity). However, the error in the restored field on the boundary surface is only proportional to an inverse power of │In∊│ (logarithmic continuity). Such a poor continuity implies some limitations on the resolution which is achievable in practice. In this case, the resolution limit is seen to be about half of the wavelength. Copyright © 1981 by The Institute of Electrical and Electronics Engineers, Inc.