Multivalent inhibition of AB5 toxins
Multivalent inhibition of AB5 toxins
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DOI：
10.1021/ja016305a
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发表时间：
2001-12-26
影响因子：
15
通讯作者：
Lees, WJ
中科院分区：
文献类型：
--
作者：
Gargano, JM;Ngo, T;Lees, WJ
蛋白质对特定碳水化合物的识别对细胞活动的调节至关重要，如受精、淋巴细胞的归巢和内吞作用的调解。不幸的是，单个糖单元和受体蛋白之间的相互作用几乎总是很弱（Ka） 103-104 M-1)。在生物系统中，这种弱结合通常通过多价相互作用增强。当一个具有多个配体的实体与另一个具有多个受体的实体结合，从而产生许多配体-受体相互作用时，就会发生多价性。多价性不仅局限于体内系统，而且通过合成轮辐系统（STARFISH/手指系统）、3,4树突状大分子、5,6和聚合物，已成功地应用于药物开发，所有这些系统都含有附着的配体的多个拷贝。本文描述了一个理论模型，用于计算合成糖共聚物与可溶性受体的多价结合增强和强多价结合。
The recognition of specific carbohydrates by proteins is essential for the regulation of cellular activity, such as fertilization, homing of lymphocytes, and mediation of endocytosis. Unfortunately, the interaction between a single sugar unit and receptor protein is almost always weak (Ka) 103-104 M-1). 1 In biological systems, this weak binding is often enhanced through multivalent interactions. 2 Multivalency occurs when one entity with multiple ligands binds to another entity with multiple receptors thus creating numerous ligand-receptor interactions. Multivalency is not limited to in vivo systems and has been applied with some success to drug development by the synthesis of hub-and-spoke systems (STARFISH/finger systems), 3, 4 dendrimers, 5, 6 and polymers, 2 all of which contain multiple copies of the ligand attached. Herein we describe a theoretical model for calculating binding enhancement due to multivalency and the strong multivalent binding of a synthetic glycopolymer to a soluble receptor,