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自组装酶纳米复合物与多肽和低分子量有机化合物:新型抗菌剂的制备、表征和应用。

Self-Assembling Enzymatic Nanocomplexes with Polypeptides and Low-Weight Organic Compounds: Preparation, Characterization, and Application of New Antibacterials.

机构信息

Faculty of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia.

Skobeltsyn Institute of Nuclear Physics, Lomonosov Moscow State University, 119991 Moscow, Russia.

出版信息

Int J Mol Sci. 2023 Jan 17;24(3):1831. doi: 10.3390/ijms24031831.

Abstract

The self-assembling of nanosized materials is a promising field for research and development. Multiple approaches are applied to obtain inorganic, organic and composite nanomaterials with different functionality. In the present work, self-assembling nanocomplexes (NCs) were prepared on the basis of enzymes and polypeptides followed by the investigation of the influence of low-molecular weight biologically active compounds on the properties of the NCs. For that, the initially possible formation of catalytically active self-assembling NCs of four hydrolytic enzymes with nine effectors was screened via molecular modeling. It allowed the selection of two enzymes (hexahistidine-tagged organophosphorus hydrolase and penicillin acylase) and two compounds (emodin and naringenin) having biological activity. Further, such NCs based on surface-modified enzymes were characterized by a batch of physical and biochemical methods. At least three NCs containing emodin and enzyme (His-OPH and/or penicillin acylase) have been shown to significantly improve the antibacterial activity of colistin and, to a lesser extent, polymyxin B towards both Gram-positive bacteria () and Gram-negative bacteria ().

摘要

纳米材料的自组装是一个有前途的研究和开发领域。多种方法被应用于获得具有不同功能的无机、有机和复合纳米材料。在本工作中,基于酶和多肽制备了自组装纳米复合物(NCs),并研究了低分子量生物活性化合物对 NCs 性质的影响。为此,通过分子建模筛选了最初可能形成具有催化活性的自组装 NCs 的四种水解酶和九种效应物。这使得可以选择两种具有生物活性的酶(六组氨酸标记的有机磷水解酶和青霉素酰化酶)和两种化合物(大黄素和柚皮素)。此外,通过一系列物理和生化方法对基于表面修饰酶的此类 NCs 进行了表征。至少有三种含有大黄素和酶(His-OPH 和/或青霉素酰化酶)的 NCs 已被证明可显著提高多粘菌素 B 和粘菌素对革兰氏阳性菌()和革兰氏阴性菌()的抗菌活性,其效果在一定程度上弱于多粘菌素 B。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e2/9915939/58434677cfab/ijms-24-01831-g001.jpg

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