The solution structure of double helical arabino nucleic acids (ANA and 2'F-ANA): effect of arabinoses in duplex-hairpin interconversion.
We report here the first structure of double helical arabino nucleic acid (ANA), the C2'-stereoisomer of RNA, and the 2'-fluoro-ANA analogue (2'F-ANA). A chimeric dodecamer based on the Dickerson sequence, containing a contiguous central segment of arabino nucleotides, flanked by two 2'-deoxy-2'F-ANA wings was studied. Our data show that this chimeric oligonucleotide can adopt two different structures of comparable thermal stabilities. One structure is a monomeric hairpin in which the stem is formed by base paired 2'F-ANA nucleotides and the loop by unpaired ANA nucleotides. The second structure is a bimolecular duplex, with all the nucleotides (2'F-ANA and ANA) forming Watson-Crick base pairs. The duplex structure is canonical B-form, with all arabinoses adopting a pure C2'-endo conformation. In the ANA:ANA segment, steric interactions involving the 2'-OH substituent provoke slight changes in the glycosidic angles and, therefore, in the ANA:ANA base pair geometry. These distortions are not present in the 2'F-ANA:2'F-ANA regions of the duplex, where the -OH substituent is replaced by a smaller fluorine atom. 2'F-ANA nucleotides adopt the C2'-endo sugar pucker and fit very well into the geometry of B-form duplex, allowing for favourable 2'F···H8 interactions. This interaction shares many features of pseudo-hydrogen bonds previously observed in 2'F-ANA:RNA hybrids and in single 2'F-ANA nucleotides.
Instituto de Química Física Rocasolano, CSIC, C/Serrano 119, 28006 Madrid, Spain.
Nerea
N
Martín-Pintado
Maryam
M
Yahyaee-Anzahaee
Ramón
R
Campos-Olivas
Anne M
AM
Noronha
Christopher J
CJ
Wilds
Masad J
MJ
Damha
Carlos
C
González
D001088:Arabinonucleotides / Q000737:chemistry*; D001089:Arabinose / Q000737:chemistry*; D020029:Base Pairing; D002236:Carbohydrate Conformation; D004247:DNA / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009841:Oligonucleotides / Q000737:chemistry
D001088:Arabinonucleotides; D009841:Oligonucleotides; D005461:Fluorine; D004247:DNA; D001089:Arabinose