含有伊米达索皮里迪尼 (IP) 单元的宏环显示增强的被动细胞透性
Bo Li1, Joshua Parker2, Skyler Briggs3
1Department of Chemistry, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, 120 Scripps Way, Jupiter, FL: 33458. USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
含有伊米达索皮里丁 (IP+) 部分的宏环 (MPs) 通过被动扩散快速进入细胞. 这一策略使MP能够准细胞内蛋白质,将其转化为生物活性抑制剂并增强治疗潜力.
科学领域:
- 药用化学 医学化学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 宏环 (MPs) 显示出针对困难蛋白质的前景,但由于膜透性差,在细胞内输送方面存在困难.
- 之前的研究表明,将一小部分伊米达索皮里迪尼 (IP+) 纳入体内可以提高被动膜透性 (PAMPA).
研究的目的:
- 为了研究IP+含有MP的细胞进入机制.
- 评估IP+修饰的MPs在向细胞内蛋白质方面的潜力.
主要方法:
- 甲基透试验 (CAPA) 用于测量细胞质透率.
- 活细胞成像,ATP消耗测定和器官细胞同位化研究.
- 评估IP+修饰的p53-MDM2抑制剂在MCF-7细胞中的生物活性.
主要成果:
- 含有IP+的MPs表现出快速的细胞质进入,与小分子相似.
- 细胞吸收主要通过被动扩散发生,绕过内体的通路.
- 对于IP+-MPs,没有观察到线粒体同局部.
- 一种IP+修饰的MP通过向p53-MDM2相互作用,成功抑制了MCF-7细胞的增殖.
结论:
- 嵌入 imidazopyridinium 是一个可行的策略,以提高宏环的细胞透性.
- 这种方法促进了针对细胞内蛋白质的MP开发,用于治疗应用.
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