具有时间分辨荧光特性的生物活性荧光探针及其在细胞成像中的应用
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- 英文论文题名：Time-resolved Fluorescence Probe with Biological Activity and its Application in Cell Imaging
- 论文作者：罗群 ; 郑伟 ; 汪福意
- 英文论文作者：Qun Luo ; Wei Zheng ; Fuyi Wang ; Institut of Chemistry ; Chinese Academy of Sciences
- 年：2016
- 作者机构：中国科学院化学研究所;
- 论文关键词：荧光探针 ; 铽 ; 时间分辨荧光 ; 分子靶向药物 ; 表皮生长因子受体EGFR
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：O657.3
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：223k
- 原文格式：D
- 会议级别：全国
摘要
将荧光基团引入到靶向药物分子中,设计合成具有靶向特异性的生物活性荧光探针,研究靶标分子的生理/病理功能,探索药物分子的作用机制已成为化学生物学研究中的热点领域。~(1-2)2003年上市的分子靶向药物吉非替尼(Gefitinib)以EGFR为靶标竞争性结合在该蛋白上的ATP结合域,干扰下游信号转导,抑制肿瘤的生长。本工作借助计算机辅助药物设计技术,将分子靶向药物Gefitinib药效骨架与含有多胺多羧酸大环螯合Tb~(3+)结构偶联,构建了一种具有时间分辨荧光特性的生物活性荧光探针(Tb-L)。该探针具有分子靶向特性,表现出高激酶抑制活性。Tb~(3+)螯合结构处于蛋白EGFR与外界溶剂的接触面上,探针分子保留了Tb~(3+)的特征发射峰,探针的荧光寿命达毫秒级,具有时间分辨荧光特征。初步的Confocal均显示探针分子主要集中在细胞膜上,为下一步深入研究探针与靶标分子EGFR的动态相互作用奠定了基础。
We have constructed a time-resolved fluorescent probe by covalently conjugate the pharmacophore of Gefitinib with Tb chromophore that is Tb~(3+) chelated by the polyamine polycarboxylic acid macrocyclic.The probe has strong EGFR protein kinase inhibitory activity.The fluorescence spectroscopy showed the probe retains the characteristic emission peak of Tb~(3+),and the lifetime of fluorescence reaches the millisecond level which can be used to time-resolved fluorescence analysis.The preliminary cell imaging showed that the probe molecules were mainly concentrated on the cell membrane,which laid the foundation for further study of the dynamic interaction between the probe and the targeted probe EGFR.
We have constructed a time-resolved fluorescent probe by covalently conjugate the pharmacophore of Gefitinib with Tb chromophore that is Tb~(3+) chelated by the polyamine polycarboxylic acid macrocyclic.The probe has strong EGFR protein kinase inhibitory activity.The fluorescence spectroscopy showed the probe retains the characteristic emission peak of Tb~(3+),and the lifetime of fluorescence reaches the millisecond level which can be used to time-resolved fluorescence analysis.The preliminary cell imaging showed that the probe molecules were mainly concentrated on the cell membrane,which laid the foundation for further study of the dynamic interaction between the probe and the targeted probe EGFR.
引文
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