2'-O-[2-(amino)-2-oxoethyl] oligonucleotides.
[structure: see text] Oligonucleotides with novel modifications, 2'-O-[2-(amino)-2-oxoethyl] (2'-O-NAc), 2'-O-[2-(methylamino)-2-oxoethyl] (2'-O-NMAc), 2'-O-[2-(dimethylamino)-2-oxoethyl] (2'-O-DMAc), and 2'-O-[2-[[2-(dimethylamino)ethyl]amino]-2-oxoethyl] (2'-O-DMAEAc), have been synthesized. These modified oligonucleotides exhibit high binding affinity to complementary RNA (and not to DNA) and considerably enhance the nuclease stability of oligonucleotides with t(1/2) > 24 h.
Prakash
Thazha P
TP
Department of Medicinal Chemistry, Isis Pharmaceuticals Inc., 2292 Faraday Avenue, Carlsbad, California 92008, USA.
Kawasaki
Andrew M
AM
Lesnik
Elena A
EA
Owens
Stephen R
SR
Manoharan
Muthiah
M
D004355:Drug Stability; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D018075:RNA, Complementary / Q000378:metabolism; D013329:Structure-Activity Relationship
D016376:Oligonucleotides, Antisense; D018075:RNA, Complementary; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I