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多功能化刷状糖聚合物,对 P-选择素具有高亲和性和抗肿瘤转移活性。

Multifunctionalized Brush-Like Glycopolymers with High Affinity to P-Selectin and Antitumor Metastasis Activity.

机构信息

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, People's Republic of China.

出版信息

Biomacromolecules. 2021 Mar 8;22(3):1177-1185. doi: 10.1021/acs.biomac.0c01689. Epub 2021 Feb 14.

Abstract

Glycopolymers that can mimic natural glycosaminoglycan, such as heparin, have shown great potentials in inhibition of cancer metastasis. In the current work, a novel series of brush-like glycopolymers (BGPs) with simultaneous functionalization of various monosaccharide or disaccharide compositions have been synthesized through a new grafting-polymerization strategy, in order to mimic the activities of both heparin and P-selectin ligand PSGL-1. In the subsequent in vitro assays of antiadhesion, platelets activation, heparanase inhibition, and so on, BGP-SFH, as one of the BGPs with the composition of the combined three sugar units, sialic acids, fucoses, and heparin disaccharides, showed the highest antimetastasis ability, similar to its prototype heparin. Moreover, in a mouse metastatic melanoma model, the BGP-SFH also inhibited B16 cell metastasis effectively. Thus, the current work not only demonstrated a type of promising antimetastasis glycopolymer BGPs, but also illustrated an easy synthetic approach to multifunctionalized glycopolymers, leading to potential applications for broader biomedical research.

摘要

能够模拟天然糖胺聚糖(如肝素)的糖聚合物在抑制癌症转移方面显示出巨大的潜力。在当前的工作中,通过一种新的接枝聚合策略,合成了一系列具有各种单糖或二糖组成的同时功能化的新型刷状糖聚合物(BGPs),以模拟肝素和 P-选择素配体 PSGL-1 的活性。在随后的抗黏附、血小板激活、肝素酶抑制等体外实验中,BGP-SFH 作为具有三种糖单元组合的 BGPs 之一,唾液酸、岩藻糖和肝素二糖,表现出最高的抗转移能力,与其原型肝素相似。此外,在小鼠转移性黑素瘤模型中,BGP-SFH 也能有效抑制 B16 细胞转移。因此,目前的工作不仅展示了一种有前途的抗转移糖聚合物 BGP,而且还说明了一种多功能化糖聚合物的简单合成方法,为更广泛的生物医学研究提供了潜在的应用。

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