Emission tuning of fluorescent kinase inhibitors: conjugation length and substituent effects.
Emission tuning of fluorescent kinase inhibitors: conjugation length and substituent effects.
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DOI：
10.1021/jo500520x
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发表时间：
2014-06-06
期刊：
影响因子：
--
通讯作者：
Wilson JN
中科院分区：
文献类型：
--
作者：
Dhuguru J;Liu W;Gonzalez WG;Babinchak WM;Miksovska J;Landgraf R;Wilson JN
据报道，针对受体酪氨酸激酶 ERBB 家族的 ATP 结合口袋的荧光 N-苯基-4-氨基喹唑啉探针。通过 TD-DFT 计算，预测通过在喹唑啉核心的 6 位上用苯基、苯乙烯基和苯基丁二烯基部分取代，用荧光团“臂”扩展芳香族喹唑啉核心，从而产生具有可调光激发能量和具有电荷转移特性的激发态的探针。光谱鉴定出几种合成探针在水溶液中不发射，并且在低极性溶剂中表现出发射增强，这表明作为开启荧光团具有良好的性能。配体诱导的 ERBB2 磷酸化测定表明，尽管对喹唑啉核心进行了化学修饰，这些探针仍然在 MCF7 细胞中发挥 ERBB2 抑制剂的作用。发现两种探针表现出 ERBB2 诱导的荧光，证明了这些探针作为开启荧光激酶抑制剂的效用。
Fluorescent N-phenyl-4-aminoquinazoline probes targeting the ATP-binding pocket of the ERBB family of receptor tyrosine kinases are reported. Extension of the aromatic quinazoline core with fluorophore “arms” through substitution at the 6- position of the quinazoline core with phenyl, styryl, and phenylbutadienyl moieties was predicted by means of TD-DFT calculations to produce probes with tunable photoexcitation energies and excited states possessing charge-transfer character. Optical spectroscopy identified several synthesized probes that are nonemissive in aqueous solutions and exhibit emission enhancements in solvents of low polarity, suggesting good performance as turn-on fluorophores. Ligand-induced ERBB2 phosphorylation assays demonstrate that despite chemical modification to the quinazoline core these probes still function as ERBB2 inhibitors in MCF7 cells. Two probes were found to exhibit ERBB2-induced fluorescence, demonstrating the utility of these probes as turn-on, fluoroescent kinase inhibitors.
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影响因子：
4
作者：
Owen, Shawn C.;Doak, Allison K.;Wassam, Pascal;Shoichet, Molly S.;Shoichet, Brian K.
通讯作者：
Shoichet, Brian K.
影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
14.8
作者：
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通讯作者：
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