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鉴定和定向开发具有明显类酶模拟特性的无机组分纳米酶用于高效前药转化。

Identification and Directed Development of Non-Organic Catalysts with Apparent Pan-Enzymatic Mimicry into Nanozymes for Efficient Prodrug Conversion.

机构信息

Department of Chemistry, Aarhus University, Aarhus, Denmark.

iNano Interdisciplinary Nanoscience Centre, Aarhus University, Aarhus, Denmark.

出版信息

Angew Chem Int Ed Engl. 2019 Jan 2;58(1):278-282. doi: 10.1002/anie.201812668. Epub 2018 Nov 28.

DOI:10.1002/anie.201812668
PMID:30408323
Abstract

Nanozymes, nanoparticles that mimic the natural activity of enzymes, are intriguing academically and are important in the context of the Origin of Life. However, current nanozymes offer mimicry of a narrow range of mammalian enzymes, near-exclusively performing redox reactions. We present an unexpected discovery of non-proteinaceous enzymes based on metals, metal oxides, 1D/2D-materials, and non-metallic nanomaterials. The specific novelty of these findings lies in the identification of nanozymes with apparent mimicry of diverse mammalian enzymes, including unique pan-glycosidases. Further novelty lies in the identification of the substrate scope for the lead candidates, specifically in the context of bioconversion of glucuronides, that is, human metabolites and privileged prodrugs in the field of enzyme-prodrug therapies. Lastly, nanozymes are employed for conversion of glucuronide prodrugs into marketed anti-inflammatory and antibacterial agents, as well as "nanozyme prodrug therapy" to mediate antibacterial measures.

摘要

纳米酶是模拟酶天然活性的纳米颗粒,在生命起源的背景下具有重要的学术意义。然而,目前的纳米酶仅模拟了哺乳动物酶的一小部分,主要是进行氧化还原反应。我们提出了一种基于金属、金属氧化物、1D/2D 材料和非金属纳米材料的非蛋白质酶的意外发现。这些发现的新颖之处在于鉴定出了具有多种哺乳动物酶明显模拟活性的纳米酶,包括独特的泛糖苷酶。进一步的新颖之处在于确定了主要候选物的底物范围,特别是在葡萄糖醛酸苷的生物转化方面,即人类代谢物和酶前药治疗领域的优势前药。最后,纳米酶被用于将葡萄糖醛酸苷前药转化为上市的抗炎和抗菌药物,以及“纳米酶前药治疗”来介导抗菌措施。

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