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银团簇酶通过抑制急性氧化应激缓解多器官损伤的配体调控催化选择性。

Ligand-Modulated Catalytic Selectivity of Ag Clusterzyme for Relieving Multiorgan Injury via Inhabiting Acute Oxidative Stress.

机构信息

Department of Physics, School of Science, Tianjin Chengjian University, Tianjin 300384, China.

Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Institute of Advanced Materials Physics, School of Science, Tianjin University, Tianjin 300350, China.

出版信息

Bioconjug Chem. 2021 Nov 17;32(11):2342-2352. doi: 10.1021/acs.bioconjchem.1c00408. Epub 2021 Oct 13.

Abstract

The artificial enzymes at the atomic level have shown great potential in chemical biology and nanomedicine, and modulation of catalytic selectivity is also critical to the application of nanozymes. In this work, atomic precision Ag clusterzymes protected by single- and dual-ligand were developed. Further, the catalytic activity and selectivity of Ag clusterzymes were modulated by adjusting doping elements and ligand. The AgPt shows more prominent antioxidant activity characteristics in the dual-ligand system, while the AgCu possesses the superoxide dismutase-like (SOD-like) activity regardless of the single- or dual-ligand system, indicating modulated catalytic selectivity. experiments showed the AgPt-D can recover radiation induced DNA damages and eliminate the excessive reactive oxygen species (ROS) generated from radiation. Subsequent radiation protection experiments reveal that AgCu-S and AgPt-D can improve the survival rate of irradiated mice from 0 to 40% and 30%, respectively. The detailed biological experiments confirm that the AgCu-S and AgPt-D can recover the SOD and 3,4-methylenedioxyamphetamine (MDA) levels via suppressing the chronic inflammation reaction. Nearly 60% of AgCu-S and AgPt-D can be excreted after a 1 day injection, and no obvious toxicological reactions were observed 30 days after injection.

摘要

在化学生物学和纳米医学领域,原子级别的人工酶显示出巨大的潜力,而纳米酶的应用关键在于调节催化选择性。在这项工作中,开发了由单配体和双配体保护的原子精度 Ag 团簇酶。此外,通过调整掺杂元素和配体来调节 Ag 团簇酶的催化活性和选择性。在双配体体系中,AgPt 表现出更显著的抗氧化活性特征,而 AgCu 无论在单配体还是双配体体系中都具有超氧化物歧化酶样(SOD 样)活性,表明催化选择性得到了调节。实验表明,AgPt-D 可以恢复辐射诱导的 DNA 损伤,并消除辐射产生的过量活性氧(ROS)。随后的辐射防护实验表明,AgCu-S 和 AgPt-D 可以分别将受辐照小鼠的存活率从 0 提高到 40%和 30%。详细的生物学实验证实,AgCu-S 和 AgPt-D 可以通过抑制慢性炎症反应来恢复 SOD 和 3,4-亚甲二氧基苯丙胺(MDA)水平。AgCu-S 和 AgPt-D 在注射后 1 天内可排出近 60%,注射 30 天后未观察到明显的毒理学反应。

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