Synthesis and Affinity Evaluation of a Small Library of Bidentate Cholera Toxin Ligands: Towards Nonhydrolyzable Ganglioside Mimics
Synthesis and Affinity Evaluation of a Small Library of Bidentate Cholera Toxin Ligands: Towards Nonhydrolyzable Ganglioside Mimics
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DOI：
10.1002/chem.200902469
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Bernardi, Anna
中科院分区：
文献类型：
--
作者：
Cheshev, Pavel;Morelli, Laura;Bernardi, Anna
合成并测试了一个小的GM1神经节苷脂不可水解模拟物库，其中含有半乳糖和唾液酸及其药效碳水化合物残基。所有的化合物都是通过高效的反应，包括点击化学协议，以及避免o -糖苷键，从现成的前体合成的。最活跃分子的Sonic还具有进一步衍生化的点，可用于缀合多价糖基。用弱亲和层析法评价了它们对霍乱毒素的亲和力，从而对最佳候选物进行了系统的评价和选择。与单个药效糖残基的亲和力相比，亲和性可提高一到两个数量级。
A small library of nonhydrolyzable mimics of GM1 ganglioside, featuring galactose and sialic acid its pharmacophoric carbohydrate residues,, was synthesized and tested. All compounds were synthesized from readily available precursors using high-performance reactions, including click chemistry protocols, and avoiding O-glycosidic bonds. Sonic of the most active molecules also feature a point of further derivatization that can be used for conjugation will, polyvalent aglycons. Their affinity towards cholera toxin was assessed by weak affinity chromatography, which allowed a systematic evaluation and selection of the best candidates. Affinity could be enhanced up to one or two orders of magnitude over the affinity of the individual pharmacophoric sugar residues.