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Structural Insights into Conformation Differences between DNA/TNA and RNA/TNA Chimeric Duplexes
Author(s) -
Anosova Irina,
Kowal Ewa A.,
Sisco Nicholas J.,
Sau Sujay,
Liao Jenyu,
Bala Saikat,
Rozners Eriks,
Egli Martin,
Chaput John C.,
Van Horn Wade D.
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600349
Subject(s) - nucleic acid , rna , dna , antiparallel (mathematics) , base pair , nucleic acid structure , chemistry , nucleic acid secondary structure , context (archaeology) , stereochemistry , nucleic acid analogue , biochemistry , helix (gastropod) , biophysics , biology , nucleic acid thermodynamics , gene , paleontology , snail , magnetic field , physics , ecology , quantum mechanics
Threose nucleic acid (TNA) is an artificial genetic polymer capable of heredity and evolution, and is studied in the context of RNA chemical etiology. It has a four‐carbon threose backbone in place of the five‐carbon ribose of natural nucleic acids, yet forms stable antiparallel complementary Watson–Crick homoduplexes and heteroduplexes with DNA and RNA. TNA base‐pairs more favorably with RNA than with DNA but the reason is unknown. Here, we employed NMR, ITC, UV, and CD to probe the structural and dynamic properties of heteroduplexes of RNA/TNA and DNA/TNA. The results indicate that TNA templates the structure of heteroduplexes, thereby forcing an A‐like helical geometry. NMR measurement of kinetic and thermodynamic parameters for individual base pair opening events reveal unexpected asymmetric “breathing” fluctuations of the DNA/TNA helix. The results suggest that DNA is unable to fully adapt to the conformational constraints of the rigid TNA backbone and that nucleic acid breathing dynamics are determined from both backbone and base contributions.