2'-O-[2-(氨基)-2-氧代乙基]寡核苷酸

2'-O-[2-(amino)-2-oxoethyl] oligonucleotides.

作者信息

Prakash Thazha P, Kawasaki Andrew M, Lesnik Elena A, Owens Stephen R, Manoharan Muthiah

机构信息

Department of Medicinal Chemistry, Isis Pharmaceuticals Inc., 2292 Faraday Avenue, Carlsbad, California 92008, USA.

出版信息

Org Lett. 2003 Feb 20;5(4):403-6. doi: 10.1021/ol027131k.

DOI:10.1021/ol027131k

PMID:12583729

Abstract

[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.

摘要

[结构：见正文] 已合成了具有新型修饰的寡核苷酸，即2'-O-[2-(氨基)-2-氧代乙基]（2'-O-NAc）、2'-O-[2-(甲氨基)-2-氧代乙基]（2'-O-NMAc）、2'-O-[2-(二甲氨基)-2-氧代乙基]（2'-O-DMAc）和2'-O-[2-[[2-(二甲氨基)乙基]氨基]-2-氧代乙基]（2'-O-DMAEAc）。这些修饰的寡核苷酸对互补RNA（而非DNA）表现出高结合亲和力，并显著提高了寡核苷酸的核酸酶稳定性，半衰期>24小时。