Solution structure of an arabinonucleic acid (ANA)/RNA duplex in a chimeric hairpin: comparison with 2 '-fluoro-ANA/RNA and DNA/RNA hybrids

Hybrids of RNA and arabinonucleic acid (ANA) as well as the 2'-fluoro-ANA a nalog (2'F-ANA) were recently shown to be substrates of the enzyme RNase H. Although RNase H binds to double-stranded RNA, no cleavage occurs with suc h duplexes. Therefore, knowledge of the structure of ANA/RNA hybrids may pr ove helpful in the design of future antisense oligonucleotide analogs. In t his study, we have determined the NMR solution structures of ANA/RNA and DN A/RNA hairpin duplexes and compared them to the recently published structur e of a 2'F-ANA/RNA hairpin duplex. We demonstrate here that the sugars of R NA nucleotides of the ANA/RNA hairpin stem adopt the C3'-endo (north, A-for m) conformation, whereas those of the ANA strand adopt a 'rigid' O4'-endo ( east) sugar pucker. The DNA strand of the DNA/RNA hairpin stem is flexible, but the average DNA/RNA hairpin structural parameters are close to the ANA /RNA and 2'F-ANA/RNA hairpin parameters. The minor groove width of ANA/RNA, 2'F-ANA/RNA and DNA/RNA helices is 9.0 +/- 0.5 Angstrom, a value that is i ntermediate between that of A- and B-form duplexes. These results rationali ze the ability of ANA/RNA and 2'F-ANA/RNA hybrids to elicit RNase H activit y.