Protecting Group Free Synthesis of Glyconanoparticles Using Amino-Oxy-Terminated Polymer Ligands.
Protecting Group Free Synthesis of Glyconanoparticles Using Amino-Oxy-Terminated Polymer Ligands.
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DOI：
10.1021/acs.bioconjchem.0c00465
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发表时间：
2020-09
影响因子：
4.7
通讯作者：
Antonio Laezza;Panagiotis G. Georgiou;Sarah-Jane Richards;Alexander N. Baker;M. Walker;M. Gibson
中科院分区：
文献类型：
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作者：
Antonio Laezza;Panagiotis G. Georgiou;Sarah-Jane Richards;Alexander N. Baker;M. Walker;M. Gibson
由于与簇糖苷效应相关的非线性增强，糖材料与碳水化合物结合蛋白的结合亲和力增强。含聚糖的金纳米颗粒尤其引起了人们的极大兴趣。这是由于它们的多功能性，其高度可调的金核（尺寸和形状），以及它们在生物传感器和诊断工具中的应用。然而，将聚糖结合到这些材料上可能具有挑战性，需要多个保护基团操作或仅使用简单的聚糖。与可以包含数百个聚糖的糖阵列相比，这导致了有限的结构多样性。本文报道了一种将无保护的聚糖偶联到末端带有氨基氧基的聚合物链上，然后将其固定在金纳米颗粒上的方法。使用同位素标记的聚糖，对该反应的效率进行了详细的探测以确认共轭，有25%的端基被功能化，主要是环封闭形式。简单的后糖基化纯化是通过简单的离心/洗涤循环来去除多余的聚糖和聚合物。这种简化的合成方法可能特别适用于使用自动化制备糖聚糖粒子库，以确定使用更传统的合成方法向前推进的命中。我们进行了凝集素结合的范例研究，以确认聚糖的结合有效性，并表明这是快速评估多价聚糖结合的有力工具。
Glycomaterials display enhanced binding affinity to carbohydrate-binding proteins due to the nonlinear enhancement associated with the cluster glycoside effect. Gold nanoparticles bearing glycans have attracted significant interest in particular. This is due to their versatility, their highly tunable gold cores (size and shape), and their application in biosensors and diagnostic tools. However, conjugating glycans onto these materials can be challenging, necessitating either multiple protecting group manipulations or the use of only simple glycans. This results in limited structural diversity compared to glycoarrays which can include hundreds of glycans. Here we report a method to generate glyconanoparticles from unprotected glycans by conjugation to polymer tethers bearing terminal amino-oxy groups, which are then immobilized onto gold nanoparticles. Using an isotope-labeled glycan, the efficiency of this reaction was probed in detail to confirm conjugation, with 25% of end-groups being functionalized, predominantly in the ring-closed form. Facile post-glycosylation purification is achieved by simple centrifugation/washing cycles to remove excess glycan and polymer. This streamlined synthetic approach may be particularly useful for the preparation of glyconanoparticle libraries using automation, to identify hits to be taken forward using more conventional synthetic methods. Exemplar lectin-binding studies were undertaken to confirm the availability of the glycans for binding and show this is a powerful tool for rapid assessment of multivalent glycan binding.