Rational Design of Silicon-Based Zinc Ionophores.
Rational Design of Silicon-Based Zinc Ionophores.
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DOI：
10.1002/anie.202201698
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发表时间：
2022-06-07
影响因子：
16.6
通讯作者：
Choudhary, Amit
中科院分区：
文献类型：
--
作者：
Yamada, Kei;Deb, Arghya;Shoba, Veronika M.;Lim, Donghyun;Maji, Basudeb;Modell, Ashley E.;Choudhary, Amit
离子载体通过生物膜传输离子，具有广泛的应用，但尚不存在其快速发展的平台。我们报告了一个平台，用于开发离子载体的金属离子螯合剂，这是很容易获得的广泛的亲和力和特异性，和结构数据，可以帮助合理的设计。具体而言，我们微调的结合亲和力和亲脂性的ZnII螯合配体通过引入甲硅烷基基团接近ZnII结合口袋，这产生的离子载体，表现优于大多数目前已知的ZnII离子载体。此外，这些基于硅的离子载体对ZnII的特异性超过其他金属，并且表现出比几种已知的ZnII离子载体（包括吡嗪）更好的抗菌活性和对哺乳动物细胞更低的毒性。这些研究建立了合理的设计原则，快速发展的有效和具体的离子载体和一类新的抗菌剂。报道了一种通过引入硅基基团来合理设计锌离子载体的一般方法。这些离子载体比几种报道的ZnII离子载体更有效。此外，这些ZnII离子载体表现出选择性抗菌活性和较低的哺乳动物细胞毒性相比，已知的离子载体，pyridine。
Ionophores transport ions across biological membranes and have wide-ranging applications, but a platform for their rapid development does not exist. We report a platform for developing ionophores from metal-ion chelators, which are readily available with wide-ranging affinities and specificities, and structural data that can aid rational design. Specifically, we finetuned the binding affinity and lipophilicity of a ZnII-chelating ligand by introducing silyl groups proximal to the ZnII-binding pocket, which generated ionophores that performed better than most of the currently known ZnII ionophores. Furthermore, these silicon-based ionophores were specific for ZnII over other metals and exhibited better antibacterial activity and less toxicity to mammalian cells than several known ZnII ionophores, including pyrithione. These studies establish rational design principles for the rapid development of potent and specific ionophores and a new class of antibacterial agents. A general approach to rationally design ZnII ionophores from ZnII chelator by incorporation of silyl-based groups is reported. These ionophores were more potent than several reported ZnII ionophores. Furthermore, these ZnII ionophores demonstrated selective antibacterial activity and lower mammalian cell toxicity compared to the known ionophore, pyrithione.
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影响因子：
15
作者：
Basa, Prem N.;Barr, Chelsea A.;Burdette, Shawn C.
通讯作者：
Burdette, Shawn C.
影响因子：
6.3
作者：
Kevin Ii DA;Meujo DA;Hamann MT
通讯作者：
Hamann MT
DOI：
10.1073/pnas.1310583110
发表时间：
2014-01-07
影响因子：
11.1
作者：
Chyan, Wen;Zhang, Daniel Y.;Radford, Robert J.
通讯作者：
Radford, Robert J.
影响因子：
4.8
作者：
Harbison-Price, Nichaela;Ferguson, Scott A.;Cook, Gregory M.
通讯作者：
Cook, Gregory M.
影响因子：
7.3
作者：
Franz, Annaliese K.;Wilson, Sean O.
通讯作者：
Wilson, Sean O.