College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
Int J Biol Macromol. 2020 Oct 1;160:26-34. doi: 10.1016/j.ijbiomac.2020.05.183. Epub 2020 May 25.
A total 68 types of marine algae oligosaccharides and polysaccharides were prepared and used to study the structure-activity relationship of oligosaccharides and polysaccharides in their interactions with fibroblast growth factors (FGF) 1 and 2. Factors considered include different types of algae, extraction methods, molecular weight, sulfate content and fractions. In the case of low molecular weight polysaccharide (SJ-D) from Saccharina japonica and its fractions eluting from anion exchange column, both 1.0 M NaCl fraction (SJ-D-I) and 2.0 M NaCl fraction (SJ-D-S) had stronger binding affinity than the parent SJ-D, suggesting that sulfated galactofucans represented the major tight binding component. Nuclear magnetic resonance showed that SJ-D-I was a typical sulfated galactofucan, composed of four units: 1, 3-linked 4-sulfated α-L-fucose (Fuc); 1, 3-linked 2, 4-disulfated α-L-Fuc; 1, 6-linked 4-sulfated β-D-Gal and/or 1, 6-linked 3, 4-sulfated β-D-Gal. Modification by autohydrolysis to oligosaccharides and desulfation decreased the FGF binding affinity while oversulfation increased the affinity. The solution-based affinities of SJ-D-I to FGF1 and FGF2 were 69 nM and 3.9 nM, suggesting that SJ-D-I showed better preferentially binding to FGF1 than a natural ligand, heparin, suggesting that sulfated galactofucan might represent a good regulator of FGF1.
共制备了 68 种海洋藻类低聚糖和多糖,并用于研究寡糖和多糖与成纤维细胞生长因子(FGF)1 和 2 相互作用的结构-活性关系。考虑的因素包括不同类型的藻类、提取方法、分子量、硫酸根含量和馏分。对于来自紫菜(Saccharina japonica)的低分子量多糖(SJ-D)及其从阴离子交换柱洗脱的馏分,1.0 M NaCl 馏分(SJ-D-I)和 2.0 M NaCl 馏分(SJ-D-S)都比母体 SJ-D 具有更强的结合亲和力,表明硫酸化半乳岩藻聚糖是主要的紧密结合成分。核磁共振表明 SJ-D-I 是一种典型的硫酸化半乳岩藻聚糖,由四个单元组成:1,3 键合的 4-硫酸化 α-L-岩藻糖(Fuc);1,3 键合的 2,4-二硫酸化 α-L-Fuc;1,6 键合的 4-硫酸化 β-D-半乳糖和/或 1,6 键合的 3,4-硫酸化 β-D-半乳糖。通过自水解修饰为低聚糖和脱硫酸化降低了 FGF 的结合亲和力,而过度硫酸化增加了亲和力。SJ-D-I 与 FGF1 和 FGF2 的基于溶液的亲和力分别为 69 nM 和 3.9 nM,表明 SJ-D-I 与 FGF1 的结合具有更好的优先选择性,优于天然配体肝素,表明硫酸化半乳岩藻聚糖可能是 FGF1 的良好调节剂。