向癌细胞中的p53通路进行传递和重新激活,使用与细胞透结合的移植循环
Grégoire Jean-Baptiste Philippe1,2, Yen-Hua Huang1, Anna Mittermeier3
1Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland 4072, Australia.
Journal of medicinal chemistry
|January 4, 2024
概括
我们通过循环化物支架增强了类药物向细胞的输送. 这改善了的吸收和活性,使得细胞内癌症相关蛋白相互作用的调制成为可能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药物运输 药物运输 药物运输
背景情况:
- 体对调节蛋白质-蛋白质相互作用有希望,但在细胞内传递方面扎.
- 针对细胞内蛋白质与蛋白质相互作用对于开发新疗法至关重要,特别是在癌症治疗中.
研究的目的:
- 为了改善阻断p53:MDM2/X相互作用的的细胞溶液输送.
- 为了利用循环作为稳定支架,以提高的输送和有效性.
主要方法:
- 一个环氧化物与一个循环细胞透 (cR10) 的结合.
- 在各种癌症细胞系中评估细胞内化,细胞内p53水平和亡诱导 (A549,MCF7,MCF10A).
- 评价膜完整性,以确保无干扰的交付.
主要成果:
- 在微分子度下,与cR10的结合显著增强了细胞内部化.
- 在接受治疗的细胞中观察到细胞内p53水平升高.
- 与之前的类似物相比,类在抑制活性和增加细胞吸收方面得到了超过35倍的改善.
- 在A549细胞中诱导了亡,而没有破坏膜.
结论:
- 成功地将一个大型极性循环输入细胞质中.
- 工程化有效调节与癌症相关的细胞内蛋白质-蛋白质相互作用.
- 这一战略为开发针对细胞内通路的基治疗方法提供了一个有前途的方法.
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