Zheng Zhen, Sun Hongbin, Hu Chen, Li Gongyu, Liu Xiaomei, Chen Peiyao, Cui Yusi, Liu Jing, Wang Junfeng, Liang Gaolin
CAS Key Laboratory of Soft Matter Chemistry, Hefei Science Center CAS, Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, China.
High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences , Hefei, Anhui 230031, China.
Anal Chem. 2016 Mar 15;88(6):3363-8. doi: 10.1021/acs.analchem.6b00036. Epub 2016 Mar 1.
Tyrosine kinase and phosphatase are two important, antagonistic enzymes in organisms. Development of noninvasive approach for sensing their activity with high spatial and temporal resolution remains challenging. Herein, we rationally designed a hydrogelator Nap-Phe-Phe(CF3)-Glu-Tyr-Ile-OH (1a) whose supramolecular hydrogel (i.e., Gel 1a) can be subjected to tyrosine kinase-directed disassembly, and its phosphate precursor Nap-Phe-Phe(CF3)-Glu-Tyr(H2PO3)-Ile-OH (1b), which can be subjected to alkaline phosphatase (ALP)-instructed self-assembly to form supramolecular hydrogel Gel 1b, respectively. Mechanic properties and internal fibrous networks of the hydrogels were characterized with rheology and cryo transmission electron microscopy (cryo-TEM). Disassembly/self-assembly of their corresponding supramolecular hydrogels conferring respective "On/Off" (19)F NMR/MRI signals were employed to sense the activity of these two important enzymes in vitro and in cell lysates for the first time. We anticipate that our new (19)F NMR/magnetic resonance imaging (MRI) method would facilitate pharmaceutical researchers to screen new inhibitors for these two enzymes without steric hindrance.
酪氨酸激酶和磷酸酶是生物体中两种重要的拮抗酶。开发一种能够以高空间和时间分辨率检测其活性的非侵入性方法仍然具有挑战性。在此，我们合理设计了一种水凝胶剂Nap-Phe-Phe(CF3)-Glu-Tyr-Ile-OH（1a），其超分子水凝胶（即凝胶1a）可受酪氨酸激酶指导进行分解，以及其磷酸前体Nap-Phe-Phe(CF3)-Glu-Tyr(H2PO3)-Ile-OH（1b），它可受碱性磷酸酶（ALP）指导进行自组装，分别形成超分子水凝胶凝胶1b。用水流变学和冷冻透射电子显微镜（cryo-TEM）对水凝胶的力学性能和内部纤维网络进行了表征。首次利用其相应超分子水凝胶的分解/自组装赋予各自的“开/关”（19）F NMR/MRI信号，在体外和细胞裂解物中检测这两种重要酶的活性。我们预计，我们新的（19）F NMR/磁共振成像（MRI）方法将有助于药物研究人员筛选这两种酶的新型无空间位阻抑制剂。
