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.
Department of Chemistry, McGill University, 801 Sherbrooke Street West, H3A 2K6, Montreal, QC, Canada.
Kyung-Lyum
KL
Min
Ekaterina
E
Viazovkina
Annie
A
Galarneau
Michael A
MA
Parniak
Masad J
MJ
Damha
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