Rational Design of Silicon-Based Zinc Ionophores.

Kei Yamada, Arghya Deb, Veronika M Shoba, Donghyun Lim, Basudeb Maji, Ashley E Modell, Amit Choudhary

Angewandte Chemie (International ed. in English) 2022 Jun 07

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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 fine-tuned 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. © 2022 Wiley-VCH GmbH.

Citation

Kei Yamada, Arghya Deb, Veronika M Shoba, Donghyun Lim, Basudeb Maji, Ashley E Modell, Amit Choudhary. Rational Design of Silicon-Based Zinc Ionophores. Angewandte Chemie (International ed. in English). 2022 Jun 07;61(23):e202201698