中国科学院上海药物研究所丁侃研究组揭示了63-Mer高支链酸性果胶多糖的精确合成及其抗肝纤维化活性。相关论文于2025年2月25日发表在《美国化学会杂志》上。

该研究团队报道了从枸杞中精确合成一种高支链酸性果胶多糖，高达63-Mer，含有10种不同的糖苷键。该合成策略依赖于高度立体选择性的正交保护十糖主干的模块化组装，通过立体控制的一锅化学选择性糖基化和氢键介导的苷元递送方法的整合高效合成三个侧链聚糖，以及通过灵活的正交保护基团操作以分支位点特异性糖基化方式聚合组装目标多糖。对合成多糖63-Mer及其短片段（9-Mer、10-Mer、11-Mer和33-Mer）的构效关系研究表明，十糖作为活性聚糖结构域具有较好的抗肝纤维化活性。

研究人员表示，天然多糖具有多种生物学功能，作为生物医学开发的候选药物越来越重要。然而，具有明确结构的多分支和大尺寸酸性多糖的可及性以及相关活性聚糖结构域的鉴定仍然具有挑战性。

附：英文原文

Title: Precision Synthesis and Antiliver Fibrosis Activity of a Highly Branched Acidic 63-Mer Pectin Polysaccharide

Author: Chaoyu Hu, Fei He, Ruixue Wu, Wanqi Zhou, Wenjing Ma, Tianhui Hao, Pengjun Cai, Farong Ye, Zhuojia Xu, Hu Zhou, Ping Wang, Kan Ding, Tiehai Li

Issue&Volume: February 25, 2025

Abstract: Natural polysaccharides possess various biological functions and have become increasingly important as drug candidates for biomedical development. However, the accessibility to multiple-branched and large-sized acidic polysaccharides with well-defined structures and the identification of related active glycan domains remain challenging. Here, we report the precision synthesis of a highly branched acidic pectin polysaccharide up to a 63-mer containing 10 different glycosidic linkages from Lycium barbarum. The synthetic strategy relies on highly stereoselective modular assembly of an orthogonally protected decasaccharide backbone, efficient synthesis of three side chain glycans by the integration of stereocontrolled one-pot chemoselective glycosylations and a hydrogen-bond-mediated aglycone delivery approach, and convergent assembly of the target polysaccharide in a branched site-specific glycosylation manner via flexible orthogonal protecting group manipulations. Structure–activity relationship studies of synthetic polysaccharide 63-mer and its short fragments (9-mer, 10-mer, 11-mer, and 33-mer) suggest that the decasaccharide as an active glycan domain exhibits better antiliver fibrosis activity.

DOI: 10.1021/jacs.4c16491

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c16491