Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, 28759, Bremen, Germany.
College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials, Ministry of Education, Nankai University, Tianjin, 300071, China.
Angew Chem Int Ed Engl. 2017 Dec 4;56(49):15742-15745. doi: 10.1002/anie.201707979. Epub 2017 Nov 6.
Phosphorylation and dephosphorylation of peptides by kinases and phosphatases is essential for signal transduction in biological systems, and many diseases involve abnormal activities of these enzymes. Herein, we introduce amphiphilic calixarenes as key components for supramolecular, phosphorylation-responsive membrane transport systems. Dye-efflux experiments with liposomes demonstrated that calixarenes are highly active counterion activators for established cell-penetrating peptides, with EC values in the low nanomolar range. We have now found that they can even activate membrane transport of short peptide substrates for kinases involved in signal transduction, whereas the respective phosphorylated products are much less efficiently transported. This allows regulation of membrane transport activity by protein kinase A (PKA) and protein kinase C (PKC), as well as monitoring of their activity in a label-free kinase assay.
磷酸化和去磷酸化肽通过激酶和磷酸酶是必不可少的信号转导在生物系统中，许多疾病涉及到这些酶的异常活动。在此，我们介绍两亲性杯芳烃作为关键组成部分的超分子，磷酸化响应的膜运输系统。用脂质体进行的染料外排实验表明，杯芳烃是高效的抗衡离子激活剂，可用于现有的穿透细胞膜肽，其 EC 值在纳摩尔级低水平。我们现在发现，它们甚至可以激活参与信号转导的激酶的短肽底物的膜转运，而相应的磷酸化产物的转运效率则要低得多。这使得可以通过蛋白激酶 A (PKA)和蛋白激酶 C (PKC)来调节膜转运活性，并且可以在无标记的激酶测定中监测它们的活性。
