Synthesis and properties of oligonucleotide chimeras containing 5'-amino-2'-deoxy-2'-fluoroarabinonucleosides.
Oligonucleotide analogues comprised of 2'-deoxy-2'-fluoro-beta-D-arabinose units joined via P3'-N5' phosphoramidate linkages (2'F-ANA(5'N)) were prepared for the first time. Among the compounds prepared were a series of 2'OMe-RNA-[GAP]-2'OMe-RNA 'chimeras', whereby the "GAP" consisted of DNA, DNA(5'N), 2'F-ANA or 2'F-ANA(5'N) segments. The chimeras with the 2'F-ANA and DNA gaps exhibited the highest affinity towards a complementary RNA target, followed by the 5'-amino derivatives, i.e., 2'F-ANA > DNA > 2'F-ANA(5'N) > DNA(5'N). Importantly, hybrids between these chimeras and target RNA were all substrates of both human RNase HII and E. coli RNase HI. In terms of efficiency of the chimera in recruiting the bacterial enzyme, the following order was observed: gap DNA > 2'F-ANA > 2'F-ANA(5'N) > DNA(5'N). The corresponding relative rates observed with the human enzyme were: gap DNA > 2'F-ANA(5'N) > 2'F-ANA > DNA(5'N).
Viazovkina
Ekaterina
E
Department of Chemistry, McGill University, Montreal, Quebec, Canada.
Min
Kyung-Lyum
KL
Galarneau
Annie
A
Damha
Masad J
MJ
D000588:Amines; D001087:Arabinonucleosides; D001483:Base Sequence; D005461:Fluorine; D006801:Humans; D007700:Kinetics; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D016914:Ribonuclease H / Q000378:metabolism*; D013379:Substrate Specificity; D013941:Thymine; D014498:Uracil
D000588:Amines; D001087:Arabinonucleosides; D009838:Oligodeoxyribonucleotides; D005461:Fluorine; D014498:Uracil; C091139:ribonuclease HII; D016914:Ribonuclease H; D013941:Thymine