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从非洲大蜗牛黏液中提取具有抗 SARS-CoV-2 活性的肝素样硫酸化多糖的纯化和特性研究。

Purification and characterisation of heparin-like sulfated polysaccharides with potent anti-SARS-CoV-2 activity from snail mucus of Achatina fulica.

机构信息

Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.

出版信息

Carbohydr Res. 2023 Jul;529:108832. doi: 10.1016/j.carres.2023.108832. Epub 2023 May 11.

Abstract

Heparin-like sulfated polysaccharide, acharan sulfate, was purified from the mucus of an African giant snail with unique sulfated glycosaminoglycans (GAGs). This study reported on finding novel and safe heparin resources from Achatina fulica for further use as well as easy isolation and purification of the active fraction from the initial raw material. Its structure was characterised by a strong-anion exchange combined with high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) spectroscopy. The results indicated that the potential acharan sulfate fraction is a glycosaminoglycan composed of several repeating disaccharide units, namely, of →4)-α-IdoA(2S)(1→4)-α-GlcNAc/GlcNAc(6S)/GlcNSO(6S)(1→, and hence, presents heterogeneity regarding negative net charge density. Furthermore, the heparinase digests inhibit the binding of SARS-CoV-2 spike protein to the ACE2 receptor. In summary, the acharan sulfate presented in this work has shown its great potential for application in the preparation of sulfated polysaccharides as an alternative to heparin with important biological activity.

摘要

从具有独特硫酸化糖胺聚糖 (GAGs) 的非洲大蜗牛的黏液中纯化出肝素样硫酸化多糖阿查兰硫酸盐。本研究报道了从褐云玛瑙螺中发现新型且安全的肝素资源,以便进一步用作肝素的替代物,同时还可以从初始原料中轻松分离和纯化活性部分。其结构通过强阴离子交换结合高效液相色谱 (HPLC) 和核磁共振 (NMR) 光谱进行了表征。结果表明,潜在的阿查兰硫酸盐部分是由几个重复的二糖单元组成的糖胺聚糖,即 →4)-α-IdoA(2S)(1→4)-α-GlcNAc/GlcNAc(6S)/GlcNSO(6S)(1→,因此,在负净电荷密度方面表现出异质性。此外,肝素酶消化物抑制 SARS-CoV-2 刺突蛋白与 ACE2 受体的结合。总之,本工作中所呈现的阿查兰硫酸盐已显示出其在制备硫酸化多糖方面的巨大应用潜力,可作为具有重要生物学活性的肝素的替代品。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b82/10174341/99c3d1c664d7/ga1_lrg.jpg

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