Oligonucleotide-europium complex conjugate designed to cleave the 5′ cap structure of the ICAM-1 transcript potentiates antisense activity in cells
Oligonucleotide-europium complex conjugate designed to cleave the 5′ cap structure of the ICAM-1 transcript potentiates antisense activity in cells
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DOI：
10.1093/nar/27.6.1547
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发表时间：
1999-03-15
影响因子：
14.9
通讯作者：
Morrow, JR
中科院分区：
文献类型：
--
作者：
Baker, BF;Lot, SS;Morrow, JR
mRNA的5‘帽结构是一个N7甲基化的鸟苷残基，通过5’-5‘三磷酸链连接到由RNA聚合酶II合成的细胞和病毒RNA的5’端。这种独特的结构促进了mRNA代谢的几个过程，包括剪接、核胞质转运、翻译起始和降解。先前的研究表明，镧系大环配合物Eu(hed)（3+）通过金属活化的配体羟乙基对三磷酸键的亲核攻击，有效地切割了溶液中mRNA的5'帽结构。该报告表明，在细胞因子处理的内皮细胞中，将Eu(hed)（3+）类似物附着在针对细胞间粘附分子1mrna的5‘端反义寡核苷酸的3’端，增强了反义寡核苷酸的抑制活性。
The 5' cap structure of mRNA is a N7 methylated guanosine residue that is linked by a 5'-5' triphosphate linkage to the 5'-terminus of cellular and viral RNAs synthesized by RNA polymerase II. This unique structure facilitates several processes of mRNA metabolism, including splicing, nucleocytoplasmic transport, initiation of translation, and degradation, Previous research has demonstrated that the lanthanide macrocycle complex, Eu(THED)(3+), effectively cleaves the 5' cap structure of mRNA in solution by nucleophilic attack of the triphosphate linkage via the metal-activated hydroxyethyl group of the THED ligand, This report shows that attachment of a Eu(THED)(3+) analog to the 3'-terminus of an antisense oligonucleotide, which targets the 5'-terminus of the intercellular adhesion molecule 1 mRNA, potentiates the inhibitory activity of the antisense oligonucleotide in cytokine-treated endothelial cells.