Differential stability of 2'F-ANA*RNA and ANA*RNA hybrid duplexes: roles of structure, pseudohydrogen bonding, hydration, ion uptake and flexibility.
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.
Watts
Jonathan K
JK
Department of Chemistry, McGill University, Montreal, QC H3A 2K6, Canada.
Martín-Pintado
Nerea
N
Gómez-Pinto
Irene
I
Schwartzentruber
Jeremy
J
Portella
Guillem
G
Orozco
Modesto
M
González
Carlos
C
Damha
Masad J
MJ
D001088:Arabinonucleotides / Q000737:chemistry*; D002412:Cations / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009691:Nucleic Acid Denaturation; D012313:RNA / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D001088:Arabinonucleotides; D002412:Cations; D014867:Water; D005461:Fluorine; D012313:RNA