2'-O-[2-[N,N-(dialkyl)aminooxy]ethyl]-modified antisense oligonucleotides.
[structure] Oligonucleotides with two novel modifications, 2'-O-¿2-[N, N-(dimethyl)aminooxy]ethyl¿ (2'-O-DMAOE) and 2'-O-¿2-[N, N-(diethyl)aminooxy]ethyl¿ (2'-O-DEAOE), have been synthesized. These modifications exhibit high binding affinity to target RNA (and not to DNA) and enhance the nuclease stability of oligonucleotides considerably with t(1/2) > 24 h as a phosphodiester.
Prakash
T P
TP
Department of Medicinal Chemistry, Isis Pharmaceuticals Inc., 2292 Faraday Avenue, Carlsbad, California 92008, USA.
Manoharan
M
M
Kawasaki
A M
AM
Lesnik
E A
EA
Owens
S R
SR
Vasquez
G
G
D018076:DNA, Complementary / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry; D012313:RNA / Q000187:drug effects; D018075:RNA, Complementary / Q000737:chemistry
D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D018075:RNA, Complementary; D012313:RNA; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I