Enhancing sequence-specific cleavage of RNA within a duplex region: incorporation of 1,3-propanediol linkers into oligonucleotide conjugates of serinol-terpyridine.
Enhancing sequence-specific cleavage of RNA within a duplex region: incorporation of 1,3-propanediol linkers into oligonucleotide conjugates of serinol-terpyridine.
复制标题
增强双链体区域内 RNA 的序列特异性切割：将 1,3-丙二醇接头掺入丝氨醇-三联吡啶的寡核苷酸缀合物。
DOI：
10.1021/bc0100197
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发表时间：
2001
影响因子：
4.7
通讯作者：
Bashkin,JK
中科院分区：
文献类型：
--
作者：
Trawick,BN;Osiek,TA;Bashkin,JK
报道了一系列新的Cu（II）-丝氨醇-三联吡啶和1，3-丙二醇的寡核苷酸缀合物的合成和RNA切割效率。这些被称为核酶模拟物的试剂被设计成在核酶模拟物-RNA双链体形成时，在RNA切割催化剂位点的正对面产生多个未配对的RNA残基。使用1，3-丙二醇接头3实现了这种设计效果，该接头模拟了天然核苷酸的5 '-和3'-羟基之间的三碳间距。在核酶模拟物DNA链中直接邻近丝氨醇-三联吡啶修饰的位置引入一个或多个这些1，3-丙二醇接头，导致互补31-mer RNA靶序列中多个磷酸的切割。这些接头有效地在RNA−DNA双链体中产生了人工错配，使得相对的RNA残基更容易通过酯交换/水解途径被切割。由各种模拟物产生的RNA切割产物与其DNA链中接头的数量和位置直接相关，并且该系列中最活跃的核酶模拟物在过量31-mer RNA靶存在下表现出多个周转。
The syntheses and RNA cleavage efficiencies of a new series of oligonucleotide conjugates of Cu(II)−serinol−terpyridine and 1,3-propanediol are reported. These reagents, termed ribozyme mimics, were designed such that they would yieldmultipleunpaired RNA residues directly opposite the site of the RNA cleavage catalyst upon ribozyme mimic−RNA duplex formation. This design effect was implemented using the 1,3-propanediol linker3, which mimics the three-carbon spacing between the 5‘- and 3‘-hydroxyls of a natural nucleotide. Incorporation of one or more of these 1,3-propanediol linkers at positions directly adjacent to the serinol−terpyridine modification in the ribozyme mimic DNA strand resulted in cleavage at multiple phosphates in a complementary 31-mer RNA target sequence. The linkers effectively created artificial mismatches in the RNA−DNA duplexes, rendering the opposing RNA residues much more susceptible to cleavage via the transesterification/hydrolysis pathway. The RNA cleavage products produced by the various mimics correlated directly with the number and locations of the linkers in their DNA strands, and the most active ribozyme mimic in the series exhibited multiple turnover in the presence of excess 31-mer RNA target.