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一种新型的软骨素 E 来源于智利帝王蟹的软骨及其抗肿瘤转移活性。

A novel chondroitin sulfate E from Dosidicus gigas cartilage and its antitumor metastatic activity.

机构信息

National Glycoengineering Research Center and Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, 72 Binhai Rd, Qingdao, 266237, People's Republic of China; State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, 271018, Shandong, People's Republic of China.

National Glycoengineering Research Center and Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, 72 Binhai Rd, Qingdao, 266237, People's Republic of China; National Engineering Laboratory for Efficient Utilization of Soil and Fertilizer Resources, National Engineering & Technology Research Center for Slow and Controlled Release Fertilizers, College of Resources and Environment, Shandong Agricultural University, Taian, Shandong, 271018, People's Republic of China.

出版信息

Carbohydr Polym. 2021 Jun 15;262:117971. doi: 10.1016/j.carbpol.2021.117971. Epub 2021 Mar 20.

DOI:10.1016/j.carbpol.2021.117971
PMID:33838835
Abstract

Chondroitin sulfate (CS) chains containing GlcUAβ1-3GalNAc(4S,6S) (E unit) have been shown to be involved in various physiological and pathological processes. However, commercial E unit-rich CS (CS-E) is difficult to produce on a large scale due to expensive and limited squid cartilage resources. In this study, a novel CS-E (CS-nE) was isolated from the cheap and abundant cartilage of the giant squid Dosidicus gigas. The CS-nE has a surprisingly large molecular mass of 696 kDa and a relatively high E unit proportion (44.5 %). It can interact with various growth factors, including HGF, bFGF, pleiotrophin, and HB-EGF, with high affinity, and exhibits dose-dependent anti-metastatic activity. Furthermore, the E unit-rich decasaccharide selectively prepared from CS-nE has been shown to be the minimal functional domain with the strongest antitumor metastatic activity. Taken together, CS-nE will be a very promising candidate for the development of CS-E-based pharmaceutical products.

摘要

硫酸软骨素(CS)链中含有 GlcUAβ1-3GalNAc(4S,6S)(E 单元),已被证明参与各种生理和病理过程。然而,由于昂贵且有限的鱿鱼软骨资源,商业上富含 E 单元的 CS(CS-E)难以大规模生产。在这项研究中,从廉价且丰富的巨型乌贼(Dosidicus gigas)软骨中分离出一种新型 CS-E(CS-nE)。CS-nE 具有令人惊讶的大分子量 696 kDa 和相对较高的 E 单元比例(44.5%)。它可以与各种生长因子(包括 HGF、bFGF、多效素和 HB-EGF)高亲和力相互作用,并表现出剂量依赖性的抗转移活性。此外,从 CS-nE 中选择性制备的富含 E 单元的十聚糖已被证明是具有最强抗肿瘤转移活性的最小功能域。总之,CS-nE 将是开发基于 CS-E 的药物产品的非常有前途的候选物。

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