Department of Chemistry, Purdue University, West Lafayette, Indiana47907, United States.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana47907, United States.
J Am Chem Soc. 2023 Jan 25;145(3):1668-1677. doi: 10.1021/jacs.2c09937. Epub 2023 Jan 14.
Multivalent interactions between carbohydrates and proteins enable a broad range of selective chemical processes of critical biological importance. Such interactions can extend from the macromolecular scale (1-10 nm) up to much larger scales across a cell or tissue, placing substantial demands on chemically patterned materials aiming to leverage similar interactions in vitro. Here, we show that diyne amphiphiles with carbohydrate headgroups can be assembled on highly oriented pyrolytic graphite (HOPG) to generate nanometer-resolution carbohydrate patterns, with individual linear carbohydrate assemblies up to nearly 1 μm, and microscale geometric patterns. These are then photopolymerized and covalently transferred to the surfaces of hydrogels. This strategy suspends carbohydrate patterns on a relatively rigid polydiacetylene (persistence length ∼ 16 nm), exposed at the top surface of the hydrogel above the bulk pore structure. Transferred patterns of appropriate carbohydrates (e.g., -acetyl-d-glucosamine, GlcNAc) enable selective, multivalent interactions ( ∼ 40 nM) with wheat germ agglutinin (WGA), a model lectin that exhibits multivalent binding with appropriately spaced GlcNAc moieties. WGA binding affinity can be further improved ( ∼ 10 nM) using diacetylenes that shift the polymer backbone closer to the displayed carbohydrate, suggesting that this strategy can be used to modulate carbohydrate presentation at interfaces. Conversely, GlcNAc-patterned surfaces do not induce specific binding of concanavalin A, and surfaces patterned with glucuronic acid, or with simple carboxylic acid or hydroxyl groups, do not induce WGA binding. More broadly, this approach may have utility in designing synthetic glycan-mimetic interfaces with features from molecular to mesoscopic scales, including soft scaffolds for cells.
糖蛋白之间的多价相互作用使广泛的选择性化学过程具有重要的生物学意义。这种相互作用可以从大分子尺度（1-10nm）扩展到跨越细胞或组织的更大尺度，这对旨在利用体外类似相互作用的化学图案材料提出了巨大的要求。在这里，我们展示了具有糖基头部的二炔双亲分子可以在高度取向的热解石墨（HOPG）上组装，以生成具有纳米分辨率的糖基图案，单个线性糖基组装体长达近 1μm，以及微尺度的几何图案。然后对这些图案进行光聚合和共价转移到水凝胶表面。这种策略将糖基图案悬浮在相对刚性的聚二乙炔（持久长度∼16nm）上，暴露在水凝胶的顶表面上方的体相孔结构之上。适当的糖基（例如，乙酰-d-葡萄糖胺，GlcNAc）的转移图案能够与麦胚凝集素（WGA）进行选择性的多价相互作用（∼40nM），WGA 是一种模型凝集素，它与适当间隔的 GlcNAc 部分表现出多价结合。使用将聚合物主链更接近所显示的糖基的二炔，可以进一步提高 WGA 的结合亲和力（∼10nM），这表明该策略可用于调节界面处的糖基呈现。相反，GlcNAc 图案化表面不会诱导伴刀豆球蛋白 A 的特异性结合，而图案化的葡萄糖醛酸、简单的羧酸或羟基表面不会诱导 WGA 结合。更广泛地说，这种方法可能在设计具有从分子到介观尺度特征的合成聚糖模拟界面方面具有实用性，包括用于细胞的软支架。
