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具有生物医学应用价值的酶活性病毒样颗粒的装饰。

Decoration of virus-like particles with an enzymatic activity of biomedical interest.

机构信息

Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico.

Department of Food Science and Biotechnology, Faculty of Chemistry, UNAM, Mexico City 04510, Mexico.

出版信息

Virus Res. 2018 Aug 15;255:1-9. doi: 10.1016/j.virusres.2018.06.014. Epub 2018 Jun 28.

DOI:10.1016/j.virusres.2018.06.014
PMID:29964063
Abstract

The natural properties of virus-like particles (VLPs), like their nanometric size, polyvalence, monodispersity and biocompatibility, had called the attention of scientists from different fields. VLPs constitute an excellent platform for the development nanomaterials with a broad spectrum of applications, ranging from physics of soft matter to the development of vaccines and biological nanocarriers. To expand the repertoire of functions of VLPs, they can be decorated with different molecules. In this research, the α-glucosidase Ima1p of Saccharomyces cerevisiae was attached to the surface of in vitro assembled VLPs of parvovirus B19, by using the SpyTag/SpyCatcher system. The resulting particles were structurally characterized displaying a noticeable increase in size compared to the non-decorated VLPs. The study of the biochemical properties of the coupled enzyme indicate that it increased its V by three-fold toward p-nitrophenyl-α-D-glucopyranoside (p-NPG) as substrate. In addition, the linked enzyme displayed a notorious 10 °C shift in its optimal temperature, from 35 °C for the non-attached enzyme, to 45 °C for the enzyme attached to VLPs. The decorated VLPs were also able to act on glycogen; therefore, these particles may be further developed as part of the therapy for treatment of lysosomal storage diseases derived from defects in the human acid α-glucosidase.

摘要

病毒样颗粒(VLPs)的天然特性,如纳米尺寸、多价性、单分散性和生物相容性,引起了来自不同领域的科学家的关注。VLPs 为开发具有广泛应用范围的纳米材料提供了一个极好的平台,从软物质物理学到疫苗和生物纳米载体的开发。为了扩展 VLPs 的功能 repertoire,可以用不同的分子对其进行修饰。在这项研究中,通过 SpyTag/SpyCatcher 系统,将酿酒酵母的α-葡萄糖苷酶 Ima1p 附着到细小病毒 B19 的体外组装 VLPs 表面。所得到的颗粒在结构上进行了表征,与未修饰的 VLPs 相比,其尺寸明显增加。对耦合酶的生化特性的研究表明,它对 p-硝基苯-α-D-葡萄糖吡喃糖苷(p-NPG)作为底物的 V 增加了三倍。此外,连接的酶在其最适温度上有一个显著的 10°C 偏移,从非附着酶的 35°C 到附着于 VLPs 的酶的 45°C。这些经过修饰的 VLPs 也能够作用于糖原;因此,这些颗粒可以进一步开发为治疗人类酸性α-葡萄糖苷酶缺陷引起的溶酶体贮积病的治疗方法的一部分。

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