Oligonucleotides comprised of alternating 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides and D-2'-deoxyribonucleosides (2'F-ANA/DNA 'altimers') induce efficient RNA cleavage mediated by RNase H.
Chimeric oligonucleotides comprised of alternating residues of 2'-deoxy-2'-fluoro-D-arabinonucleic acid (2'F-ANA) and DNA were synthesized and evaluated for an important antisense property-the ability to elicit ribonuclease H (RNase H) degradation of complementary RNA. Experiments used both human RNase HII and Escherichia coli RNase HI. Mixed backbone oligomers comprising alternating three-nucleotide segments of 2'F-ANA and three-nucleotide segments of DNA were the most efficient at eliciting RNase H degradation of target RNA, and were significantly better than oligonucleotides entirely composed of DNA, suggesting that these mixed backbone oligonucleotides may be potent antisense agents.
Min
Kyung-Lyum
KL
Department of Chemistry, McGill University, 801 Sherbrooke Street West, H3A 2K6, Montreal, QC, Canada.
Viazovkina
Ekaterina
E
Galarneau
Annie
A
Parniak
Michael A
MA
Damha
Masad J
MJ
D001087:Arabinonucleosides / Q000737:chemistry*; D006868:Hydrolysis; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism*; D016914:Ribonuclease H / Q000378:metabolism*
D001087:Arabinonucleosides; D016376:Oligonucleotides, Antisense; D012313:RNA; D016914:Ribonuclease H