A critical survey of the structure-function of the antisense oligo/RNA heteroduplex as substrate for RNase H

被引:101
作者
Zamaratski, E [1 ]
Pradeepkumar, PI [1 ]
Chattopadhyaya, J [1 ]
机构
[1] Univ Uppsala, Ctr Biomed, Dept Bioorgan Chem, S-75123 Uppsala, Sweden
来源
JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS | 2001年 / 48卷 / 03期
关键词
structure; DNA/RNA hybrid; AONs; RNase H;
D O I
10.1016/S0165-022X(01)00149-X
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The aim of this review is to draw a correlation between the structure of the DNA/RNA hybrid and its properties as a substrate for the RNase H, as well as to point the crucial structural requirements for the modified AONs to preserve their RNase H potency. The review is divided into the following parts: (1) mechanistic considerations, (2) target RNA folding-AON folding-RNase H assistance in AON/RNA hybrid formation, (3) carbohydrate modifications, (4) backbone modifications, (5) base modifications, (6) conjugated AONs, (7) importance of the tethered chromophore in AON for the AON/RNA hybrid interactions with the RNase H. The structural changes in the AON/RNA hybrid duplexes brought by different modifications of the sugar, backbone or base in the antisense strand, and the effect of these changes on the RNase H recognition of the modified substrates have been addressed. Only those AON modifications and the corresponding AON/RNA hybrids, which have been structurally characterized by spectroscopic means and functionally analyzed by their ability to elicit RNase H potency in comparison with the native counterpart have been presented here. (C) 2001 Published by Elsevier Science B.V.
引用
收藏
页码:189 / 208
页数:20
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