Synthesis of antisense oligonucleotides with minimum depurination

被引:15
作者
Krotz, AH [1 ]
Cole, DL [1 ]
Ravikumar, VT [1 ]
机构
[1] ISIS Pharmaceut, Carlsbad, CA 92008 USA
关键词
antisense oligonucleotide; DMTr removal; depurination;
D O I
10.1081/NCN-120019499
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
The removal of 4,4'-dimethoxytrityl (DMTr) groups from oligonucleotides at low pH and the acid lability of the glycosidic linkage of purine nucleotides constitute an inherent conflict in preparative oligonucleotide chemistry. The use of a mildly acidic NaOAc buffer (10 mM, pH 3.0-3.2) allows adjustment of the pH in a range where the progress of the DMTr removal reaction can be monitored conveniently by HPLC and the optimum reaction time can be calculated. As a result, oligonucleotides with minimum depurination are obtained.
引用
收藏
页码:129 / 134
页数:6
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