FACILE PREPARATION OF NUCLEASE RESISTANT 3' MODIFIED OLIGODEOXYNUCLEOTIDES

被引:128
作者
GAMPER, HB
REED, MW
COX, T
VIROSCO, JS
ADAMS, AD
GALL, AA
SCHOLLER, JK
MEYER, RB
机构
[1] MicroProbe Corportion, Bothell, WA 98021
关键词
D O I
10.1093/nar/21.1.145
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
An efficient chemical procedure for the immobilization of carboxylate containing conjugate groups onto controlled pore glass (CPG) is described. The derivatized supports were used in the automated synthesis of an oligodeoxynucleotide (20-mer ODN) containing a 3' phosphodiester linked hexanol, aminohexyl, acridine, or cholesterol group. The stability of the oligomer in a hepatoma cell culture was found to be prolonged two to three fold by the presence of any one of the 3' tails. By contrast, an aminohexyl group appended to the 5' terminus of the ODN only marginally improved its nuclease resistance. These data support the notion that antisense ODNs are primarily degraded by 3' exonucleases. Introduction of simple 3' tails which incorporate a normal phosphodiester linkage can increase ODN stability by interfering with these enzymes.
引用
收藏
页码:145 / 150
页数:6
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