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Surface plasmon resonance imaging of glycoarrays identifies novel and unnatural carbohydrate-based ligands for potential ricin sensor development

机译:糖基的表面等离子共振成像识别新的和非天然的基于碳水化合物的配体,用于潜在的蓖麻毒素传感器开发

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摘要

Carbohydrate microarrays provide access to high through-put analysis of protein–carbohydrate interactions. Herein we demonstrate the use of SPR imaging (SPRi) of glycoarrays to assess the ligand specificity of the reputedly galactose-specific plant lectin RCA (Ricinus communis agglutinin 120), a surrogate for the bioterrorism agent ricin. Glycoarray studies identified RCA120 ligands based on galactose substituted at the 6-position with sialic acid. These observations, which were confirmed by saturation transfer difference (STD) NMR spectroscopy studies, inspired the synthesis of non-natural 6-substituted galactose derivatives, which were shown to have ~3–4 fold enhanced binding to RCA with respect to the unsubstituted compound. These novel unnatural galactosides, which are chemically and biologically more robust than their natural glycan counterparts, represent new potential ligands for the development of carbohydrate-based ricin sensors.ud
机译:碳水化合物微阵列可提供蛋白质与碳水化合物相互作用的高通量分析。本文中,我们证明了使用糖阵列的SPR成像(SPRi)来评估据说是半乳糖特异性植物凝集素RCA(Ricinus communis凝集素120)的配体特异性,这是生物恐怖药蓖麻毒蛋白的替代品。糖阵列研究鉴定了基于半乳糖的唾液酸取代的RCA120配体。这些观察结果通过饱和转移差异(STD)NMR光谱学研究得到证实,激发了非天然6取代半乳糖衍生物的合成,与未取代化合物相比,它们显示出与RCA的结合力提高了约3-4倍。这些新颖的非天然半乳糖苷在化学和生物学上比天然的聚糖更强健,它们代表了开发基于碳水化合物的蓖麻毒蛋白传感器的新的潜在配体。

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