Abstract:
The multivalent presentation of glycans leads to enhanced binding avidity to lectins due to the cluster glycoside effect. Most materials used as scaffolds for multivalent glycan arrays, such as polymers or nanoparticles, have intrinsic dispersity: meaning that in any sample, a range of valencies are presented and it is not possible to determine which fraction(s) are responsible for binding. The intrinsic dispersity of many multivalent glycan scaffolds also limits their reproducibility and predictability. Here we make use of the structurally programmable nature of self-assembled metal coordination cages, with polyhedral metal-ion cores supporting ligand arrays of predictable sizes, to assemble a 16-membered library of perfectly monodisperse glycoclusters displaying valencies from 2 to 24 through a careful choice of ligand/metal combinations. Mono- and trisaccharides are introduced into these clusters, showing that the synthetic route is tolerant of biologically relevant glycans, including sialic acids. The cluster series demonstrates increased binding to a range of lectins as the number of glycans increases. This strategy offers an alternative to current glycomaterials for control of the valency of three-dimensional (3-D) glycan arrays, and may find application across sensing, imaging, and basic biology.
摘要:
由于簇糖苷效应,聚糖的多价呈递导致与凝集素的结合亲合力增强。大多数材料用作多价聚糖阵列的支架,如聚合物或纳米颗粒,具有内在分散性:这意味着在任何样本中,呈现了一系列的化合价,并且不可能确定哪些部分负责结合。许多多价聚糖支架的固有分散性也限制了它们的可重复性和可预测性。在这里,我们利用自组装金属配位笼的结构可编程性质,多面体金属离子核支持可预测大小的配体阵列,通过仔细选择配体/金属组合,组装显示2至24价的完美单分散糖簇的16元库。将单糖和三糖引入这些簇中,表明合成路线对生物相关的聚糖具有耐受性,包括唾液酸。簇系列表明随着聚糖数量的增加,与一系列凝集素的结合增加。该策略为当前的糖材料提供了一种替代方案,用于控制三维(3-D)聚糖阵列的效价。并可能在传感中找到应用,成像,和基础生物学。