结构上定义的氨酸八糖化域用于结合SARS-CoV-2 Omicron BA.4/BA.5/BA.5.2尖端蛋白 RBD
Zizhe An1, Changkai Bu1, Deling Shi1
1National Glycoengineering Research Center, Shandong University, No. 72, Binhai Road, Qingdao, Shandong Province 266237, China.
International journal of biological macromolecules
|December 30, 2023
概括
氨酸寡糖体对SARS-CoV-2尖端蛋白具有强烈的结合,其中八糖体表现出最高的亲和力. 这项研究为开发针对COVID-19的基于氨酸的抗病毒药物铺平了道路.
科学领域:
- 生物化学 生物化学
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
背景情况:
- 肝素是一种高度负电荷的生物分子,对于预防SARS-CoV-2感染至关重要.
- 肝素竞争性地与病毒尖端蛋白结合,阻止其与细胞肝素硫酸盐共受体的相互作用.
研究的目的:
- 为了结构性地描述针对SARS-CoV-2尖端蛋白质-赫巴兰硫酸盐相互作用的氨酸寡糖.
- 为了确定具有高结合亲和度的特定肝素结构,开发新型抗病毒药物.
主要方法:
- 肝酶I消化以制备肝寡合物 (dp ≥4).
- 亲和和大小排除色谱用于分离寡糖.
- 用于结构和序列分析的HILIC-ESI-FTMS和SAX染色学.
- 分子对接以研究结合机制.
主要成果:
- 肝素八糖与六糖和四糖相比,对Omicron尖端蛋白受体结合域 (RBD) 的结合亲和力显著更高.
- 一种特定的八糖化物,[ΔUA-GlcNS6S-GlcA-GlcNS6S-IdoA2S-GlcNS6S-IdoA2S-GlcNS6S],具有12个硫酸盐组,对RBD具有很高的结合.
- 在RBD中,分子对接揭示了八糖糖的硫酸盐/碳酸组和基本氨基酸残留物 (Arg403,Arg452,Arg493,His505) 之间的关键相互作用,其最佳结合亲和力为-6.8 kcal/mol.
结论:
- 从结构上定义的氨酸寡糖,特别是八糖,具有强大的结合能力,以SARS-CoV-2尖端蛋白RBD.
- 这些发现支持对精确定义的氨酸寡糖的潜在开发,作为有效的抗SARS-CoV-2疗法.
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