通过 lysine dendron 结合传递向核的蛋白质
Ling Xiang1, Dongmei Qi1, Lan Yang1
1Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China. fengxuli@cqu.edu.cn.
Chemical communications (Cambridge, England)
|July 1, 2025
概括
这项研究介绍了一种使用 lysine dendrons (LDs) 将蛋白质输送到细胞核的新方法. 这种方法增强了蛋白质输送和抗瘤效果,为先进的蛋白质疗法提供了一个有前途的平台.
科学领域:
- 生物结合化学 生物结合化学
- 药物输送系统 药物输送系统
- 分子治疗学分子治疗学
背景情况:
- 针对性地将治疗性蛋白质输送到细胞核仍然是药物开发中的一个重大挑战.
- 现有的蛋白质输送方法通常需要复杂的表面修改,并且缺乏效率.
- 克服这些局限性对于推进基于蛋白质的疗法至关重要.
研究的目的:
- 引入一种新的 lysine dendron (LD) 中介策略,以有效地向核向蛋白质输送.
- 证明多价值LD蛋白结构在增强细胞吸收和核积累方面的有效性.
- 评估LD修饰蛋白的治疗潜力,特别是RNase A,用于癌症治疗.
主要方法:
- 使用点击化学将 lysine dendrons (LDs) 与蛋白质结合起来.
- 开发用于增强生物相互作用的多价值LD蛋白架构.
- 评估细胞吸收和核定位的LD-修饰蛋白质体外.
- 在体外和体内评估LD修饰的RNase A的抗瘤疗效.
主要成果:
- 氨酸树突结合显著增强了细胞吸收和蛋白质的核积累.
- 与未经修改的RNase A相比,LD修改的RNase A表现出优越的核发射能力.
- 在体外和体内活体模型中观察到LD修饰的RNase A具有显著的抗瘤疗效.
- 证实了LD蛋白结合的生物可逆性.
结论:
- 氨酸树突介导的蛋白质结合是一种有效的策略,用于核向的输送.
- 这种方法为开发下一代蛋白疗法提供了一个多功能和高效的平台.
- 开发的生物可逆策略克服了传统蛋白质输送系统的局限性.
相关概念视频
01:45Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
01:34Nuclear Protein Sorting
4.8K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.8K
01:36Delivery Pathways to the Lysosome
7.3K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
7.3K
01:46Nuclear Localization Signals and Import
6.0K
Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
6.0K