Polyvalent binding to carbohydrates immobilized on an insoluble resin
Polyvalent binding to carbohydrates immobilized on an insoluble resin
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DOI：
10.1073/pnas.94.20.10554
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发表时间：
1997-09-30
影响因子：
11.1
通讯作者：
Kahne, D
中科院分区：
文献类型：
--
作者：
Liang, R;Loebach, J;Kahne, D
许多研究已经确定，多价性是细胞表面碳水化合物识别的关键特征。然而，碳水化合物-蛋白质相互作用通常通过使用专注于单价碳水化合物配体在溶液中的行为的测定来评估。一般认为，溶液中单价碳水化合物配体的相对亲和力与其多价亲合力相关。在本文中，我们表明，直接在TentaGel珠上合成的碳水化合物配体以多价方式与碳水化合物结合蛋白相互作用。因此，碳水化合物衍生的珠子可以用作细胞表面的模型系统，以评估多价碳水化合物-蛋白质相互作用。通过使用组合方法来合成多价碳水化合物的固相文库，可以快速解决细胞表面碳水化合物识别领域的关键问题。例如，本文报道的研究表明，在涉及多价碳水化合物的识别过程中存在意想不到的特异性程度。然而，多价亲合力和溶液亲合力之间的相关性较差。显然，碳水化合物在聚合物表面的呈现对配体与蛋白质受体的相互作用具有深远的影响。这些发现对于碳水化合物在自然界中如何作为识别信号以及如何研究多价碳水化合物-蛋白质相互作用具有重要意义。
Numerous studies have established that polyvalency is a critical feature of cell surface carbohydrate recognition. Nevertheless, carbohydrate-protein interactions are typically evaluated by using assays that focus on the behavior of monovalent carbohydrate ligands in solution. It has generally been assumed that the relative affinities of monovalent carbohydrate ligands in solution correlate viith their polyvalent avidities. In this paper we show that carbohydrate ligands synthesized directly on TentaGel beads interact with carbohydrate-binding proteins in a polyvalent manner. The carbohydrate-derivatized beads can, therefore, be used as model systems for cell surfaces to evaluate polyvalent carbohydrate-protein interactions. By using a combinatorial approach to synthesize solid-phase libraries of polyvalent carbohydrates, one can rapidly address key issues in the area of cell surface carbohydrate recognition. For example, studies reported herein demonstrate that there is an unanticipated degree of specificity in recognition processes involving polyvalent carbohydrates. However, the correlation between polyvalent avidities and solution affinities is poor. Apparently, the presentation of carbohydrates on the polymer surface has a profound influence on the interaction of the Ligand with the protein receptor. These findings have implications for how carbohydrates function as recognition signals in nature, as well as for how polyvalent carbohydrate-protein interactions should be studied.