Department of Chemistry and Chemical Engineering, Physical Chemistry, Chalmers University of Technology, 41296, Göteborg, Sweden.
Department of Chemistry and Molecular Biology, University of Gothenburg, 41296, Göteborg, Sweden.
Angew Chem Int Ed Engl. 2019 Oct 14;58(42):15000-15004. doi: 10.1002/anie.201909536. Epub 2019 Sep 5.
The development of a fluorescent LCK inhibitor that exhibits favourable solvatochromic properties upon binding the kinase is described. Fluorescent properties were realised through the inclusion of a prodan-derived fluorophore into the pharmacophore of an ATP-competitive kinase inhibitor. Fluorescence titration experiments demonstrate the solvatochromic properties of the inhibitor, in which dramatic increase in emission intensity and hypsochromic shift in emission maxima are clearly observed upon binding LCK. Microscopy experiments in cellular contexts together with flow cytometry show that the fluorescence intensity of the inhibitor correlates with the LCK concentration. Furthermore, multiphoton microscopy experiments demonstrate both the rapid cellular uptake of the inhibitor and that the two-photon cross section of the inhibitor is amenable for excitation at 700 nm.
描述了一种荧光 LCK 抑制剂的开发，该抑制剂在与激酶结合时表现出有利的溶剂化变色性质。荧光性质是通过将 prodan 衍生的荧光团纳入 ATP 竞争性激酶抑制剂的药效团来实现的。荧光滴定实验证明了抑制剂的溶剂化变色性质，在与 LCK 结合时，明显观察到发射强度的剧烈增加和发射峰的蓝移。细胞环境中的显微镜实验以及流式细胞术表明，抑制剂的荧光强度与 LCK 浓度相关。此外，多光子显微镜实验表明，抑制剂的快速细胞摄取以及抑制剂的双光子截面可在 700nm 处激发。
