作为向细胞输送蛋白质的通用方式
Kathleen H Ngo1,2, Max E Distler1,2, Michael Evangelopoulos3,2
1Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.
Journal of the American Chemical Society
|January 15, 2025
概括
改善蛋白质输入细胞需要创建混合的DNA树突蛋白结构. 与传统的球状核酸 (proSNA) 纳米结构相比,这些新型结构显著增强了细胞吸收.
科学领域:
- 生物结合化学
- 纳米技术
- 细胞生物学
背景情况:
- 细胞内蛋白质的传递对于探针和疗法至关重要,但由于细胞吸收不足而受到阻碍.
- 目前的方法,如球形核酸 (proSNA) 纳米构造,由于受限的DNA负载和表面修饰而面临限制.
- 众所周知,DNA密度和序列会影响捕食器受体参与和细胞内化.
研究的目的:
- 开发一种使用混合DNA树突蛋白架构增强细胞内蛋白质传递的新方法.
- 将这些新架构的细胞吸收效率与传统的proSNA进行比较.
- 研究DNA序列和结合方法对细胞内化的影响.
主要方法:
- 合成的分支DNA树突与二环基因组进行点击化学.
- 用亚-氨酸进行生物对称的工程蛋白质.
- 开发了一种基于lysine的表面树突结合而无突变的可通用方法.
- 使用各种蛋白质大小的蛋白质-DNA树突结构与proSNAs的细胞吸收比较.
主要成果:
- 与均分布的proSNA相比,蛋白-DNA树突结构显示出更优越和更快速的细胞内化.
- 吸收效率受到DNA序列的影响,富含关氨酸 (G) 的树突比富含提氨酸 (T) 的树突更能进入细胞.
- 可通用结合方法使细胞蛋白质 (42-464 kDa) 的摄取量增加了多达17倍.
结论:
- 混合DNA树突蛋白架构为改善细胞内蛋白质递送提供了高度有效的策略.
- 局部DNA呈现和特定的寡核酸序列显著增强细胞吸收.
- 这种方法为蛋白质生物结合提供了一个多功能和高效的平台,克服了先前方法的局限性.
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