Differential stability of 2’F-ANA*RNA and ANA*RNA hybrid duplexes: roles of structure, pseudohydrogen bonding, hydration, ion uptake and flexibility.
|Title||Differential stability of 2’F-ANA*RNA and ANA*RNA hybrid duplexes: roles of structure, pseudohydrogen bonding, hydration, ion uptake and flexibility.|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Watts, Jonathan K., Martín-Pintado Nerea, Gómez-Pinto Irene, Schwartzentruber Jeremy, Portella Guillem, Orozco Modesto, González Carlos, and Damha Masad J.|
|Journal||Nucleic Acids Res|
|Date Published||2010 Apr|
|Keywords||Arabinonucleotides, Biomolecular, Cations, Fluorine, Hydrogen Bonding, Models, Molecular, Nuclear Magnetic Resonance, Nucleic Acid Denaturation, RNA, Thermodynamics, Water|
Hybrids of RNA with arabinonucleic acids 2’F-ANA and ANA have very similar structures but strikingly different thermal stabilities. We now present a thorough study combining NMR and other biophysical methods together with state-of-the-art theoretical calculations on a fully modified 10-mer hybrid duplex. Comparison between the solution structure of 2’F-ANA*RNA and ANA*RNA hybrids indicates that the increased binding affinity of 2’F-ANA is related to several subtle differences, most importantly a favorable pseudohydrogen bond (2’F-purine H8) which contrasts with unfavorable 2’-OH-nucleobase steric interactions in the case of ANA. While both 2’F-ANA and ANA strands maintained conformations in the southern/eastern sugar pucker range, the 2’F-ANA strand’s structure was more compatible with the A-like structure of a hybrid duplex. No dramatic differences are found in terms of relative hydration for the two hybrids, but the ANA*RNA duplex showed lower uptake of counterions than its 2’F-ANA*RNA counterpart. Finally, while the two hybrid duplexes are of similar rigidities, 2’F-ANA single strands may be more suitably preorganized for duplex formation. Thus the dramatically increased stability of 2’F-ANA*RNA and ANA*RNA duplexes is caused by differences in at least four areas, of which structure and pseudohydrogen bonding are the most important.