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作为多价值莱克-碳水化合物结合的多功能探针的甘-金纳米粒子:阻断病毒感染和纳米粒子组装的影响

Darshita Budhadev¹, Emma Poole¹, Inga Nehlmeier²

¹School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.

Journal of the American Chemical Society

|September 16, 2020

概括

含有甘氨酸的金纳米颗粒揭示了病原体如何结合细胞. 这有助于设计糖结合物来阻断乳素-糖的相互作用,并防止像埃博拉病毒这样的感染.

科学领域:

生物化学
生物物理
纳米技术

背景情况:

在生物学和病原体感染中,多价值的莱克-甘氨酸相互作用至关重要.
由于未知的乳素结构和重叠的特异性,设计特定的葡萄糖结合物来抑制这些相互作用是具有挑战性的.
传统方法缺乏有效的抑制剂设计所需的结构洞察力.

研究的目的:

开发金纳米颗粒 (GNP) 作为机械探测器,用于研究多价值莱克-甘氨酸相互作用.
区分密切相关的讲解蛋白的结合机制 (DC-SIGN和DC-SIGNR).
建立莱克-甘氨酸组合形成的预测模型及其治疗含义.

主要方法:

使用金纳米颗粒 (GNP) 显示密集的甘氨酸层.
使用光灭方法量化结合亲和度.
结合水力动态尺寸分析和电子显微镜来研究莱克结合模式.
引入组合形成潜力 (PAF) 预测术语.

主要成果:

这些GNP有效量化了结合亲和关系,并揭示了DC-SIGN和DC-SIGNR的独特结合机制.
DC-SIGN同时与一个GNP结合,而DC-SIGNR则与多个GNP进行交叉连接.
在PAF术语成功预测了组装结果.
GNP- glycans强烈抑制了DC- SIGN介导的埃博拉病毒的进入 (IC50降至95 pM),但仅部分抑制了DC- SIGNR.

结论:

黄金纳米颗粒作为强大的探针来剖析复杂的莱克-甘氨酸相互作用.
对于有效抑制病毒感染而言,同时封锁所有乳素结合部位至关重要.
了解莱克结合方式是设计有效的葡萄糖结合物治疗方法的关键.

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