Journal of Medicinal Chemistry p. 831 - 841 (1993)
Update date:2022-08-04
Topics:
Kawasaki
Casper
Freier
Lesnik
Zounes
Cummins
Gonzalez
Cook
'Uniformly' modified phosphodiester or phosphorothioate oligonucleotides incorporating 2'-deoxy-2'-fluoroadenosine, -guanosine, -uridine, and - cytidine, reported herein for the first time, when hybridized with RNA afforded consistent additive enhancement of duplex stability without compromising base-pair specificity. CD spectra of the 2'-deoxy-2'-fluoro- modified oligonucleotides hybridized with RNA indicated that the duplex adopts a fully A-form conformation. The 2'-deoxy-2'-fluoro-modified oligonucleotides in phosphodiester form were not resistant to nucleases; however, the modified phosphorothioate oligonucleotides were highly nuclease resistant and retained exceptional binding affinity to the RNA targets. The stabilizing effects of the 2'-deoxy-2'-fluoro modifications on RNA-DNA duplexes were shown to be superior to those of the 2'-O-methylribo substitutions. RNA hybrid duplexes with uniformly 2'-deoxy-2'-fluoro-modified oligonucleotides did not support HeLa RNase H activity; however, incorporation of the modifications into 'chimeric' oligonucleotides has been shown to activate mammalian RNase H. 'Uniformly' modified 2'-deoxy-2'-fluoro phosphorothioate oligonucleotides afforded antisense molecules with (1) high binding affinity and selectivity for the RNA target and (2) stability toward nucleases.
View MoreTaizhou Huading Chemical Co.,Ltd
Contact:+86-576-88583898
Address:Economic&Technology development zone,Taizhou City,Zhejiang Province,China
RongCheng Tianyu Technology Co.,Ltd.
Contact:86-631-7519595
Address:220Ping Donghai Road RongChengCity,ShangDong Province China
Guangzhou Flower's Song Fine Chemical CO,. Ltd
Contact:+86-20-87475199
Address:No.12, Fenghuang 3 Road, Jiulong Industrial Park, Luogang District, Guangzhou. China
Contact:+86 512 6287 2180
Address:398 Ruoshui Road, Suzhou Industrial Park, Suzhou, Jiangsu, P. R. China
Zhonghao (dalian) Research and Design Institute of Chemical Industry Co., Ltd
Contact:+86 411 84674606
Address:201, Huangpu Road , Shahekou District, Dalian ,116023-China
Doi:10.1016/j.bmcl.2016.08.097
(2016)Doi:10.1002/chem.201402124
(2014)Doi:10.1055/s-0031-1290326
(2012)Doi:10.1002/chem.201102207
(2012)Doi:10.1016/0008-6215(91)89007-3
(1991)Doi:10.1021/jo3003562
(2012)