The reactivity of phosphodiester bonds within linear single-stranded oligoribonucleotides is strongly dependent on the base sequence

The reactivity of phosphodiester bonds within linear single-stranded oligoribonucleotides is strongly dependent on the base sequence
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DOI:
10.1093/nar/30.2.468
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发表时间:
2002-01-15
影响因子:
14.9
通讯作者:
Lönnberg, H
Lönnberg, H
中科院分区:
生物学2区
文献类型:
--
作者:
Kaukinen, U;Lyytikäinen, S;Lönnberg, H

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已在 pH 8.5 和 35°C 下研究了仅含有一个反应性核糖核苷单元(所有其他核苷均为 2'-O-甲基化)的短嵌合寡核苷酸的裂解。在没有表现出任何形成确定的二级结构的趋势的20个不同序列中,可断裂的5'-UpA-3'和5'-CpA-3'磷酸二酯键分别经历>100倍和高达35倍的反应性差异。与二核苷一磷酸相比,观察到速率加速和延迟超过一个数量级。即使单个碱基的几个核苷远离易裂键的变化也会显着影响反应速率。还研究了易裂键 3'-和/或 5'-侧的双链体形成。并观察到具有强烈的速率延迟作用。讨论了磷酸二酯键对分子环境高度敏感的起源。
The cleavage of short chimeric oligonucleotides containing only one reactive ribonucleoside unit, all other nucleosides being 2'-O-methylated, has been studied at pH 8.5 and 35degreesC. Among the 20 different sequences that, did not exhibit any tendency to: form a defined secondary structure, the scissile 5'-UpA-3' and 5'-CpA-3' phosphodiester bonds experienced >100- and up to 35-fold reactivity differences, respectively. Compared with dinucleoside monophosphates, both rate accelerations and retardations of more than one order of magnitude were observed. Even a change of a single base several nucleosides away from the scissile bond markedly affected the reaction rate. Duplex formation at the 3'- and/or 5'-side of the scissile bond was also studied. and observed to be strongly rate retarding. The origin of the high sensitivity of phosphodiester bonds to the molecular environment is discussed.