Murthy Bandaru Narasimha, Voelcker Nicolas Hans, Jayaraman Narayanaswamy
School of Chemistry, Physics, and Earth Sciences, Flinders University, Adelaide 5001, Australia.
Glycobiology. 2006 Sep;16(9):822-32. doi: 10.1093/glycob/cwl014. Epub 2006 Jun 16.
It is established that achieving higher binding affinities in carbohydrate-protein interactions requires multivalent presentations of the sugar ligands at the receptor binding site. Several inhibition, calorimetric, mass balance, and other studies have reiterated the beneficial effects of molecular level clustering of the sugar ligands for tight binding to the receptors. We have undertaken an effort to study the multivalent effects involving larger assemblies, represented by micelles, and their lectin interactions. The micelles were constituted with monomer bearing one- or two-sugar moieties at the monomolecular level and with varying the distances between the sugar moieties. Micellar aggregation studies and dynamic light scattering (DLS) studies afforded details of the aggregation numbers and the hydrodynamic diameters of various glycolipid (GL) micelles. The GL micelles were used as analytes of surface plasmon resonance (SPR) experiments on a lectin concanavalin A (Con A)-immobilized surface. SPR studies of the micelle-lectin interactions demonstrate that the ligand-receptor binding can be fit into the bivalent analyte model of interaction. Furthermore, micelles formed from two-sugar containing GLs are able to elicit favorable kinetic association rate constants in comparison to the micelles constituted with one-sugar containing GLs. The kinetic rate constants across the micelles and the effect of the sugar valencies in the GLs are discussed.
已证实，在碳水化合物 - 蛋白质相互作用中实现更高的结合亲和力需要在受体结合位点多价呈现糖配体。多项抑制、量热、质量平衡及其他研究反复强调了糖配体分子水平聚集对于与受体紧密结合的有益作用。我们致力于研究涉及以胶束为代表的更大聚集体的多价效应及其与凝集素的相互作用。这些胶束由在单分子水平上带有一个或两个糖部分的单体构成，且糖部分之间的距离各不相同。胶束聚集研究和动态光散射（DLS）研究提供了各种糖脂（GL）胶束的聚集数和流体动力学直径的详细信息。这些GL胶束被用作在固定有凝集素伴刀豆球蛋白A（Con A）的表面上进行表面等离子体共振（SPR）实验的分析物。胶束与凝集素相互作用的SPR研究表明，配体 - 受体结合可符合二价分析物相互作用模型。此外，与由含一个糖的GL构成的胶束相比，由含两个糖的GL形成的胶束能够产生有利的动力学缔合速率常数。讨论了胶束间的动力学速率常数以及GL中糖价态的影响。
