开发化学修饰的氧化还原响应蛋白作为智能治疗药物。
Developing chemically modified redox-responsive proteins as smart therapeutics.
机构信息
Department of Chemistry, Renmin University of China, Beijing 100872, China.
出版信息
Chem Commun (Camb). 2019 Apr 25;55(35):5163-5166. doi: 10.1039/c9cc00519f.
The conditional control of protein function in response to the physiological changes of diseased cells is essential to develop smart protein therapeutics. Herein, we report a redox-responsive chemical modification of a protein by conjugating an intracellular glutathione (GSH)-cleavable ligand, NSA, onto a protein residue. We demonstrated that the NSA conjugation of Ribonuclease A (RNase A) enabled the control of the protein function by GSH in an aqueous solution and living cells, with extended applications for targeted cancer therapy using a lipid nanoparticle-based intracellular protein delivery strategy.
为了开发智能蛋白质疗法，对响应病变细胞的生理变化的蛋白质功能进行条件控制是至关重要的。在此，我们通过将细胞内谷胱甘肽（GSH）可裂解配体 NSA 连接到蛋白质残基上，报告了一种蛋白质的氧化还原响应性化学修饰。我们证明了通过 GSH 在水溶液和活细胞中对核糖核酸酶 A（RNase A）进行 NSA 缀合，能够控制蛋白质的功能，并且可以使用基于脂质纳米颗粒的细胞内蛋白质递药策略扩展用于靶向癌症治疗的应用。
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