变型受体金属离子荧光探针开发及活体细胞荧光成像应用

项目名称： 变型受体金属离子荧光探针开发及活体细胞荧光成像应用

项目编号： No.21276251

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 化学工业

项目作者： 徐兆超

作者单位： 中国科学院大连化学物理研究所

项目金额： 80万元

中文摘要： 荧光探针检测活体细胞内金属离子的分布和浓度变化对理解细胞内金属离子稳态具有极其重要意义。然而小分子金属离子荧光探针在结合选择性方面存在难以克服的缺陷，比如由于人造受体构型和结合方式一定，探针只能依靠金属离子自身的配位能力不同而表现出结合选择性。为了对配位不利的目标金属离子具有特异的结合选择性，受体最好能够对客体具有区别于一般的结合方式。换句话说，受体能够针对不同的金属离子变换构型来提高结合选择性，即变型受体。最近申请人利用酰胺的互变异构作为变型因子来设计变型受体ZTF（JACS,2010,601），发现ZTF以酰胺的形式结合其他金属离子，而对锌离子却是以其亚胺酸的形式结合并表现出对最大结合力。本研究以此为基础开发一系列ZTF衍生的近红外锌离子变型荧光探针，研究锌离子在不同细胞的亚细胞器中的分布和浓度变化。并以变型受体为核心思想开发其他金属离子变型受体荧光探针。

中文关键词： 荧光探针；变型受体；酰胺互变异构；结合选择性；荧光强度提高

英文摘要： Fluorescent probes to interrogate metal ion availability and spatial distribution as well as concentration within living cells would greatly advance our understanding of cellular metal homestasis.However, specific binding selectivity for interest metal ions is still a challenge for fluorescent probe design.The lower affinity of most reported probes for target results from the moderate coordination nature of target metal ion with the chelators, which have a defined coordination pattern and show larger affinities to these competitive metal ions.Most receptors in existing host-guest chemistry have a confined binding 'cavity'. Due to a single binding pattern, high specificity to an analyte is extremely difficult to achieve. In order to make analyte-binding specific and more favorable, it would be beneficial if the binding pattern of the receptor with analyte is different from that with other competitors. In other words, the receptor is transformable to bind the analyte of choice, that is transformable receptors.In our previous study, we find tautomerization may play the role of a transformable factor (JACS,2010,601). The amide-containg DPA receptor ZTF and naphthalimide-derived fluorescent probe ZTRS show extreme selectivity for Zn2+. The specificity for Zn2+ comes from its different binding modes to metal ions, i.e

英文关键词： Fluorescent Probes；Transformable Receptors；Amide Tautermerization；Binding Selectivity；Improvement of Fluorescence Intensity