Andersen Kristen A, Smith Thomas P, Lomax Jo E, Raines Ronald T
Graduate Program in Molecular and Cellular Pharmacology, University of Wisconsin-Madison , 1300 University Avenue, Madison, Wisconsin 53706, United States.
Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.
ACS Chem Biol. 2016 Feb 19;11(2):319-23. doi: 10.1021/acschembio.5b00966. Epub 2015 Dec 15.
The use of exogenous proteins as intracellular probes and therapeutic agents is in its infancy. A major hurdle has been the delivery of native proteins to an intracellular site of action. Herein, we report on a compact delivery vehicle that employs the intrinsic affinity of boronic acids for the carbohydrates that coat the surface of mammalian cells. In the vehicle, benzoxaborole is linked to protein amino groups via a "trimethyl lock." Immolation of this linker is triggered by cellular esterases, releasing native protein. Efficacy is demonstrated by enhanced delivery of green fluorescent protein and a cytotoxic ribonuclease into mammalian cells. This versatile strategy provides new opportunities in chemical biology and pharmacology.
将外源性蛋白质用作细胞内探针和治疗剂的研究尚处于起步阶段。一个主要障碍是将天然蛋白质递送至细胞内作用位点。在此，我们报道了一种紧凑的递送载体，它利用硼酸对覆盖哺乳动物细胞表面的碳水化合物的固有亲和力。在该载体中，苯并氧杂硼烷通过“三甲基锁”与蛋白质氨基相连。这种连接子的裂解由细胞酯酶触发，从而释放天然蛋白质。绿色荧光蛋白和一种细胞毒性核糖核酸酶向哺乳动物细胞的增强递送证明了其有效性。这种通用策略为化学生物学和药理学提供了新的机遇。
