Enhancement of ribozyme catalytic activity by a contiguous oligodeoxynucleotide (facilitator) and by 2'-O-methylation.

Enhancement of ribozyme catalytic activity by a contiguous oligodeoxynucleotide (facilitator) and by 2'-O-methylation.
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通过连续寡脱氧核苷酸(促进剂)和 2-O-甲基化增强核酶催化活性。

DOI:
10.1093/nar/20.17.4607
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发表时间:
1992
影响因子:
14.9
通讯作者:
Goodchild,J
Goodchild,J
中科院分区:
生物学2区
文献类型:
--
作者:
Goodchild,J

文献摘要

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设计用于切割病毒RNA特有序列的RNA催化剂(核酶)可能被开发为治疗剂。为此,它们需要高催化效率和对核酸酶的抗性。这里报告的是两种方法,可以结合使用,以提高这些性能。首先,可以通过与核酶的3′-末端邻接地结合到底物上的寡核苷酸(促进剂)来提高催化效率。第二,核酶侧翼序列的2′-O-甲基化增加了催化活性以及对核酸酶的抗性。与促进剂寡脱氧核苷酸组合,切割速率比未修饰的核酶增加20倍。
RNA catalysts (ribozymes) designed to cleave sequences unique to viral RNA's might be developed as therapeutics. For this purpose, they would require high catalytic efficiency and resistance to nucleases. Reported here are two approaches that can be used in combination to improve these properties. First, catalytic efficiency can be improved by oligonucleo tides (facilitators) that bind to the substrate contiguously with the 3′-end of the ribozyme. Second, 2′-O-methylation of flanking sequences of the ribozyme increases catalytic activity as well as resistance to nucleases. In combination with a facilitator oligodeoxynucleotide, the cleavage rate was increased 20 fold over that of the unmodified ribozyme.