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动机定向氧化折叠用于设计和发现用于蛋白质识别的多循环

¹The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Accounts of chemical research

|March 14, 2025

概括

研究人员使用新型动机开发了二硫化物导向的多环 (DDMP). 这些DDMP为药物发现提供了更大的结构多样性和耐受性,超越了天然基架.

科学领域:

生物化学和分子生物学
药用化学医学化学
类治疗药物类治疗药物

背景情况:

由于高效的残留物利用和稳定的结构,多环对蛋白质具有优势.
富含二硫化物 (DRPs) 是一个重要的类别,但结构多样性有限,阻碍了治疗开发.
现有的DRP支架对于广泛的连接体和治疗应用是不够的.

研究的目的:

开发一种设计和发现具有新结构和新功能的DRP的新方法.
克服天然DPR支架在联体和药物发现中的局限性.
创建多样化的DRP,增强稳定性和序列操纵耐受性.

主要方法:

使用二硫化物导向基因 (双氨酸和三氨酸) 引导氧化折叠.
引入了基因定向氧化折叠的概念,用于构建具有多重二硫化键的.
采用生物显示系统,如菌体显示,生成和选大型的随机DDMP库.

主要成果:

开发了二硫化物导向的多环 (DDMP),具有精确的二硫化物配对和对序列变化的高耐受性.
通过改变二硫化物导向动图,氨酸模式和链接器长度来设计多种DDMP.
发现了具有独特3D结构和对细胞表面受体 (例如瘤抗原,GPCRs) 的高亲和力/特异性的DDMPs.

结论:

基因定向的氧化折叠可以创建超越自然支架的新型DRP.
DDMPs是一个突破,为联体和治疗开发提供了一个新的平台.
这种方法有助于发现用于生物分析,化学生物学和生物医学的.

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