Peptide-substituted oligonucleotide synthesis and non-toxic, passive cell delivery.

Peptide-substituted oligonucleotide synthesis and non-toxic, passive cell delivery.
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DOI:
10.1038/sigtrans.2016.19
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发表时间:
2016
影响因子:
39.3
通讯作者:
Caruthers MH
Caruthers MH
中科院分区:
医学1区
文献类型:
--
作者:
Shang S;Monfregola L;Caruthers MH

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已知化学修饰的寡脱氧核苷酸(ODNs)通过与RNA相互作用来调节基因表达。已经开发了一种用于合成氨基酸或肽取代的三唑基膦酸酯类似物(TP ODN)的有效方法,以提供改善的稳定性和细胞摄取。化学性质是相当普遍的,因为肽可以在任何预先选择的核苷酸间连接处引入整个TP ODN。这些合成的TP ODN在没有转染试剂的情况下通过内吞作用进入细胞并定位于核周细胞器中。通过用内体释放剂处理,包埋的ODN被释放到细胞质中,然后有几种作为microRNA抑制剂具有活性。
Chemically modified oligodeoxynucleotides (ODNs) are known to modulate gene expression by interacting with RNA. An efficient approach for synthesizing amino acid- or peptide-substituted triazolylphosphonate analogs (TP ODNs) has been developed to provide improved stability and cell uptake. The chemistry is quite general, as peptides can be introduced throughout the TP ODN at any preselected internucleotide linkage. These synthetic TP ODNs enter cells through endocytosis in the absence of transfection reagents and localize into perinuclear organelles. The entrapped ODNs are released into the cytoplasm by treatment with endosomal-releasing agents and several are then active as microRNA inhibitors.
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