氨基酸残留驱动的纳米粒子向蛋白质腔:表面化学要求超越尺寸补充性的结合特异性
Fangfang Liu1,2, Guofang Zhang1,2, Xiaofeng Wang1,2
1Laboratory of Inflammation and Vaccines, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 518055 Shenzhen, China.
Journal of the American Chemical Society
|January 7, 2026
概括
纳米颗粒 (NP) 可以向以前被认为是无法治疗的蛋白质腔. 氧化NP (CeO2NPs) 和黄金NP (AuNPs) 与SARS-CoV-2尖端剪切剂的结合方式不同,揭示了选择性NP结合的残留水平识别.
科学领域:
- 生物物理
- 纳米技术
- 病毒学
背景情况:
- 具有大或浅腔的蛋白质相互作用接口是小分子药物具有挑战性的目标.
- 纳米颗粒 (NP) 提供了针对这些"无毒"部位的潜力.
- SARS-CoV-2 尖端 (S) 蛋白质剪切剂具有适合NP相互作用的可访问腔.
研究的目的:
- 调查控制纳米粒子向蛋白质腔的因素.
- 将氧化纳米颗粒 (CeO2NPs) 和黄金纳米颗粒 (AuNPs) 与SARS-CoV-2 S三元体的结合选择性和机制进行比较.
- 阐明NP表面化学如何影响可访问腔内的特定蛋白质残留物的相互作用.
主要方法:
- 使用尺寸匹配的CeO2NP和金纳米粒子 (AuNP) 进行比较分析.
- 使用生物层干扰测量来评估NP与S的结合.
- 在中部和侧面的S剪切腔中研究了NP蛋白相互作用的残留水平.
主要成果:
- 虽然CeO2NPs和AuNPs都与S trimer结合,但它们具有不同的结合特征.
- CeO2NPs选择性地向受体结合域 (RBD) 中心腔,与Asp残留物相互作用.
- 优选与富含Arg的图案相互作用的AuNP侧腔,包括S1/S2裂纹部位.
结论:
- 纳米颗粒与蛋白质腔的结合是由残留水平的识别决定的,而不仅仅是尺寸的兼容性.
- CeO2NP利用与Asp残留物的协调来稳定结合,而AuNP则使用与Arg残留物的静电吸引.
- 这种理解使得纳米颗粒的合理设计能够选择性地向治疗应用的缩蛋白质特征.
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