Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India.
Chem Soc Rev. 2009 Dec;38(12):3463-83. doi: 10.1039/b815961k. Epub 2009 Aug 17.
Studying the weak binding affinities between carbohydrates and proteins has been a central theme in sustained efforts to uncover intricate details of this class of biomolecular interaction. The amphiphilic nature of most carbohydrates, the competing nature of the surrounding water molecules to a given protein receptor site and the receptor binding site characteristics led to the realization that carbohydrates are required to exert favorable interactions, primarily through clustering of the ligands. The clustering of sugar ligands has been augmented using many different innovative molecular scaffolds. The synthesis of clustered ligands also facilitates fine-tuning of the spatial and topological proximities between the ligands, so as to allow the identification of optimal molecular features for significant binding affinity enhancements. The kinetic and thermodynamic parameters have been delineated in many instances, thereby allowing an ability to correlate the multivalent presentation and the observed ligand-receptor interaction profiles. This critical review presents various multivalent ligands, synthetic and semisynthetic, and mechanisms by which the weak binding affinities are overcome, and the ligand-receptor complexation leads to significantly enhanced binding affinities (157 references).
研究碳水化合物与蛋白质之间的弱结合亲和力一直是揭示这类生物分子相互作用复杂细节的持续努力的核心主题。大多数碳水化合物的两亲性、周围水分子对给定蛋白质受体部位的竞争性质以及受体结合部位的特征，使得人们认识到碳水化合物需要发挥有利的相互作用，主要是通过配体的聚集。已经使用许多不同的创新分子支架来增强糖配体的聚集。聚集配体的合成也便于在配体之间精细调整空间和拓扑接近性，从而能够确定用于显著提高结合亲和力的最佳分子特征。在许多情况下已经描绘了动力学和热力学参数，从而能够将多价呈现与观察到的配体-受体相互作用谱相关联。这篇批判性综述介绍了各种多价配体，包括合成和半合成的，以及克服弱结合亲和力的机制，以及配体-受体络合导致显著增强的结合亲和力（157 个参考文献）。
