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整体化方法揭示硫酸软骨素的奥秘:表面电荷、结构与生长因子结合的相关性。

A holistic approach to unravelling chondroitin sulfation: Correlations between surface charge, structure and binding to growth factors.

机构信息

Departamento de Química Bioorgánica, Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.

Laboratorio de Química Neuro-Regenerativa, Hospital Nacional de Parapléjicos, SESCAM, Finca la Peraleda s/n, 45071, Toledo, Spain.

出版信息

Carbohydr Polym. 2018 Dec 15;202:211-218. doi: 10.1016/j.carbpol.2018.08.120. Epub 2018 Aug 30.

DOI:10.1016/j.carbpol.2018.08.120
PMID:30286994
Abstract

Chondroitin sulfate (CS) is a relevant family of polysaccharides that participates in a large variety of biological events that are related to neural processes by regulating various growth factors through the pattern and degree of sulfation of the polysaccharide. However, their own complexity makes their optimization for biomedical applications a difficult undertaking. Thus, a different perspective has to be taken. Herein, we show that the particular sulfate distribution within the disaccharide repeating-unit plays a key role in the binding of growth factors (GFs). In particular, this disposition modulates the surface charge of the helical structure that, interestingly, has a significant influence on the binding capacity of CSs with several GFs. This fact should be carefully considered in the design of new ligands with improved activity as GFs ligands.

摘要

硫酸软骨素(CS)是一种相关的多糖家族,通过调节各种生长因子的模式和程度的多糖硫酸化,参与与神经过程相关的多种生物事件。然而,它们自身的复杂性使得它们在生物医学应用中的优化成为一项艰巨的任务。因此,必须采取不同的视角。在这里,我们表明二糖重复单元内特定的硫酸盐分布在生长因子(GFs)的结合中起着关键作用。特别是,这种排列方式调节了螺旋结构的表面电荷,有趣的是,这对 CS 与几种 GFs 的结合能力有显著影响。在设计具有更好 GF 配体活性的新型配体时,应该仔细考虑这一事实。

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