Synthesis and photophysical properties of a fluorescent cyanoquinoline probe for profiling ERBB2 kinase inhibitor response.
Synthesis and photophysical properties of a fluorescent cyanoquinoline probe for profiling ERBB2 kinase inhibitor response.
复制标题
用于分析 ERBB2 激酶抑制剂反应的荧光氰基喹啉探针的合成和光物理性质。
DOI：
10.1016/j.bmc.2017.09.034
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发表时间：
2017
影响因子：
3.5
通讯作者：
Wilson,JamesN
中科院分区：
文献类型：
--
作者：
Lee,Heajin;Landgraf,Ralf;Wilson,JamesN
A fluorescent probe targeting the ERBB2 receptor tyrosine was designed, synthesized and evaluated as reporter of ERBB2 dynamics in overexpressing BT474, i.e. Her2(+), cells. Two cyanoquinazoline (CQ) probes modeled after type-I (CQ1) or active state and type-II (CQ2) or inactive state inhibitors were designed and synthesized with extended π systems that impart binding-induced, turn-on fluorescence. Solution spectroscopy revealed thatCQ1exhibited attractive photophysical properties and displayed turn-on emission in the presence of purified, soluble ERBB2 kinase domain, whileCQ2was found to be non-emissive, likely due to quenching via a photoinduced electron transfer mechanism. Live cell imaging withCQ1revealed that this probe targeted an intracellular population of ERBB2, which increased following treatment with type-I inhibitors, gefinitib and canertinib, but showed no response to type-II inhibitors.CQ1thus provides a novel means of imaging the dynamic response of ERBB2(+) cells to kinase inhibitors.
