MODIFIED OLIGONUCLEOTIDES IN RABBIT RETICULOCYTES - UPTAKE, STABILITY AND ANTISENSE PROPERTIES

被引：22

作者：

BOIZIAU, C

TOULME, JJ

机构：

[1] Laboratoire de Biophysique, INSERM U201, Muséum National d'Historie Naturelle, 75005 Paris, 43, rue Cuvier

来源：

BIOCHIMIE | 1991年 / 73卷 / 11期

关键词：

OLIGODEOXYRIBONUCLEOTIDES; TRANSLATION INHIBITION;

D O I：

10.1016/0300-9084(91)90171-V

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have investigated the behaviour of antisense oligonucleotides in rabbit reticulocytes. Both backbone-modified oligomers (methyl-phosphonate and phosphorothioate analogues), anomers of nucleotide units (alpha) and oligonucleotides linked to various ligands (intercalator, polylysine, dodecanol) were tested with respect to cellular uptake and inhibition of protein synthesis. Oligonucleotides added at an external concentration of 10-mu-M slowly entered the cell up to a concentration of a few hundred nanomolars. A large fraction of phosphorothioate analogues was found to be associated with the membrane. Alpha-, methylphosphonate and phosphorothioate analogues remained intact during the incubation with reticulocytes although the latter were partly dephosphorylated. Antisense oligonucleotides were targeted against three different sites of the rabbit beta-globin mRNA: the 5' end of the message, the initiator AUG or the coding sequence. No specific effect on beta-globin synthesis was observed with any of the investigated compounds.

引用

页码：1403 / 1408

页数：6

共 33 条

[11]

CHANG EH, 1989, ANTI-CANCER DRUG DES, V4, P221

[12] PRIMARY STRUCTURE OF RABBIT BETA-GLOBIN MESSENGER-RNA AS DETERMINED FROM CLONED DNA [J].