Department of Chemistry and Biochemistry, Biomolecular Sciences Institutes, Florida International University, 11200 SW 8th St., Miami, FL 33199, USA.
Department of Natural and Applied Sciences, Florida International University, 11200 SW 8th St., Miami, FL 33199, USA.
Angew Chem Int Ed Engl. 2022 Mar 14;61(12):e202116722. doi: 10.1002/anie.202116722. Epub 2022 Jan 20.
Despite the high potential of controlling cellular processes and treating various diseases by intracellularly delivered proteins, current delivery systems exhibit poor efficiency due to poor serum stability, cellular entry, and cytosolic availability of proteins. Here, we report a novel functional group, phenyl carbamoylated guanidine (Ph-CG), that greatly enhances the delivery efficiency to various types of cells. Owing to the substantially lowered pK , the hydrophobic Ph-CG offers optimized inter-macromolecular interactions via enhanced hydrogen-bonding and hydrophobic interactions. The coplanarity of Ph-CG also leads to the better intracellular entry of protein complexes. Intracellularly delivered apoptosis-inducing enzymes and antibodies significantly induce cell viability inhibitions in a serum-containing medium. The newly developed Ph-CG can be introduced to various existing carriers, leading to the realization of future therapeutic protein delivery.
尽管通过细胞内递送来控制细胞过程和治疗各种疾病具有很大的潜力，但由于蛋白质在血清中的稳定性差、细胞进入和细胞质中的可用性差，目前的递送系统效率低下。在这里，我们报告了一种新型的功能基团，苯甲酰基胍（Ph-CG），它大大提高了各种类型细胞的递送效率。由于 pK 值显著降低，疏水性的 Ph-CG 通过增强氢键和疏水相互作用提供了优化的大分子间相互作用。Ph-CG 的共面性也导致蛋白质复合物更好地进入细胞内。在含有血清的培养基中，细胞内递送来的诱导细胞凋亡的酶和抗体显著抑制细胞活力。新开发的 Ph-CG 可以引入到各种现有的载体中，从而实现未来的治疗性蛋白质递送。
