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Target Self-Enhanced Selectivity in Metal-Specific DNAzymes.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2019-12-22 , DOI: 10.1002/anie.201915675
Po-Jung Jimmy Huang 1 , Donatien de Rochambeau 2 , Hanadi F Sleiman 2 , Juewen Liu 1
Affiliation  

Highly selective recognition of metal ions by rational ligand design is challenging, and simple metal binding by biological ligands is often obscured by nonspecific interactions. In this work, binding-triggered catalysis is used and metal selectivity is greatly increased by increasing the number of metal ions involved, as exemplified in a series of in vitro selected RNA-cleaving DNAzymes. The cleavage junction is modified with a glycyl-histidine-functionalized tertiary amine moiety to provide multiple potential metal coordination sites. DNAzymes that bind 1, 2, and 3 Zn2+ ions, increased their selectivity for Zn2+ over Co2+ ions from approximately 20-, 1000-, to 5000-fold, respectively. This study offers important insights into metal recognition by combining rational ligand design and combinatorial selection, and it provides a set of new DNAzymes with excellent selectivity for Zn2+ ions.

中文翻译:

金属特异性DNA酶的目标自我增强选择性。

通过合理的配体设计高度选择性地识别金属离子是一项挑战,而生物配体的简单金属结合常常因非特异性相互作用而被掩盖。在这项工作中,使用了结合触发的催化作用,并且通过增加所涉及的金属离子的数量极大地提高了金属选择性,如一系列体外选择的裂解RNA的DNA酶所举例说明的。切割连接被甘氨酰-组氨酸官能化的叔胺部分修饰,以提供多个潜在的金属配位位点。结合1、2和3个Zn2 +离子的DNA酶,相对于Co2 +离子,其对Zn2 +的选择性分别增加了约20倍,1000倍至5000倍。这项研究结合了合理的配体设计和组合选择,为金属识别提供了重要的见识,
更新日期:2020-01-23
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