The solution structure of double helical arabino nucleic acids (ANA and 2′F-ANA): effect of arabinoses in duplex-hairpin interconversion

Abstract

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.