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Saikat Mandal¹, Jeremy L Ritchey¹, Prabhat Bhat¹

¹Department of Chemistry and Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43210, United States.

|March 11, 2026

概括

研究人员开发了BCP16e,这是一种具有低+2电荷的新型细胞透 (CPP). 这种最低充电的CPP提高了细胞内传输效率和安全性,克服了传统高充电CPP的局限性.

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:

细胞透 (CPPs) 促进生物分子的细胞内传递.
传统的CPP通常需要高的正电荷 (+6或更高),导致毒性和非目标效应.
在保持效率的同时,最大限度地降低CPP费用是一个关键的挑战.

研究的目的:

为了优化双循环 bismuth-mediated CPP,BCP16,以改善细胞内传递.
为了研究电荷密度和CPP效率之间的关系.
开发一种更安全,低电荷的CPP,以提高细胞吸收率.

主要方法:

对 BCP16.16 的结构-活动关系 (SAR) 分析.
药物化学优化. 药物化学的优化.
对BCP16及其类似物BCP16e进行交付效率,蛋白质溶解稳定性和安全性的比较分析.

主要成果:

发现了BCP16e,它是一种强大的CPP模拟物,在生理pH下具有+2电荷.
与母体BCP16.6相比,BCP16e显示出显著更高的细胞质进入效率.
BCP16e保持了类似的蛋白质溶解稳定性,并表现出更好的安全性.

结论:

高电离子电荷对于高效的CPP介导细胞转移并不重要.
充电最小的CPP可以实现高传递效率,降低毒性.
BCP16e为设计更安全,更有效的细胞内输送工具提供了一个有前途的框架.

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