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Rational Design of Silicon-Based Zinc Ionophores.

ABSTRACT: 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 Zn^II -chelating ligand by introducing silyl groups proximal to the Zn^II -binding pocket, which generated ionophores that performed better than most of the currently known Zn^II ionophores. Furthermore, these silicon-based ionophores were specific for Zn^II over other metals and exhibited better antibacterial activity and less toxicity to mammalian cells than several known Zn^II 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.

SUBMITTER: Yamada K

PROVIDER: S-EPMC9527067 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Rational Design of Silicon-Based Zinc Ionophores.

Yamada Kei K Deb Arghya A Shoba Veronika M VM Lim Donghyun D Maji Basudeb B Modell Ashley E AE Choudhary Amit A

Angewandte Chemie (International ed. in English) 20220406 23

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 Zn<sup>II</sup> -chelating ligand by introducing silyl groups proximal to the Zn ...[more]

PMID: 35385189

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