Surface plasmon resonance imaging of glycoarrays identifies novel and unnatural carbohydrate-based ligands for potential ricin sensor development
Surface plasmon resonance imaging of glycoarrays identifies novel and unnatural carbohydrate-based ligands for potential ricin sensor development
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DOI：
10.1039/c1sc00120e
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发表时间：
2011-01-01
期刊：
影响因子：
8.4
通讯作者：
Field, Robert A.
中科院分区：
文献类型：
--
作者：
Fais, Margherita;Karamanska, Rositsa;Field, Robert A.
碳水化合物微阵列为蛋白质-碳水化合物相互作用的高通量分析提供了途径。在这里，我们证明了使用SPR成像（SPRi）的糖阵列，以评估配体的特异性，据说半乳糖特异性植物凝集素RCA（120）（蓖麻凝集素120），生物恐怖主义代理蓖麻毒素的替代品。糖阵列研究鉴定了基于在6位被唾液酸取代的半乳糖的RCA（120）配体。通过饱和转移差（STD）NMR光谱研究证实的这些观察启发了非天然6-取代的半乳糖衍生物的合成，其显示相对于未取代的化合物具有类似于3-4倍增强的与RCA（120）的结合。这些新的非天然半乳糖苷，这是化学和生物学上更强大的比他们的天然聚糖对应物，代表了新的潜在配体的发展碳水化合物为基础的蓖麻毒素传感器。
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(120) (Ricinus communis agglutinin 120), a surrogate for the bioterrorism agent ricin. Glycoarray studies identified RCA(120) 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 similar to 3-4 fold enhanced binding to RCA(120) 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.