半胱氨酸及同型半胱氨酸高选择性双光子荧光探针及其在活细胞成像中的应用

项目名称： 半胱氨酸及同型半胱氨酸高选择性双光子荧光探针及其在活细胞成像中的应用

项目编号： No.51273107

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 一般工业技术

项目作者： 于晓强

作者单位： 山东大学

项目金额： 80万元

中文摘要： 半胱氨酸（Cys）与同型半胱氨酸（Hcy）同时表达在真核细胞内，结构上只有一个亚甲基的差别，但功能不同：Cys是构成蛋白质和谷胱甘肽的氨基酸；Hcy与人类的心血管疾病、进行性老年痴呆症有直接关联。高选择性地分别实现Cys及Hcy的细胞内荧光成像具有重要的分子细胞生物学意义。针对目前高选择性识别并成像细胞内Cys的荧光探针尚不成熟、识别并成像细胞内Hcy的荧光探针尚无报导、高选择性识别并利用双光子荧光显微镜成像细胞内Cys的双光子荧光探针刚刚起步的状态，结合申请人的工作基础提出本课题。本课题将以具有活细胞通透性的水溶性双光子材料为基础研制含醛双光子荧光探针，通过调整探针分子的电子结构、引入中间体干扰基团等技术实现探针对Cys及Hcy的高选择性识别。课题将提供具有高选择性成像活细胞内Cys及Hcy潜力的双光子荧光探针并利用双光子荧光显微镜实现其在活细胞中荧光成像。

中文关键词： 荧光探针；半胱氨酸/同型半胱氨酸；双光子荧光成像；细胞器超微结构；高选择性

英文摘要： Cysteine (Cys) and Homocysteine (Hcy) are expressed in eukaryotic cells simultaneously, and there only is a nuance in a methylene. But the tiny difference leads to a significantly different function:Cys is a amino acid which constructs proteins and glutathione; while excess of Hcy was shown to be a risk factor for cardiovascular and Alzheimer's diseases.Thus it has important value in molecular cell biology to highly selectively give separate fluorescent imaging of intracellular Cys and/or Hcy.Due to the juvenility of fluorescent probes which can separately probe and bioimage intracellular Cys with high selectivity, the lack of fluorescent sensors for Hcy which possesses not only the high selectivity but also performance imaging intracellular Hcy and the infantility of two-photon fluorescent probes for Cys with high selectivity and by which the fluorescent imaging can be given in two-photon fluorescent microscopy, the project has been applied on the basis of proposer's previous works. On the basis of two-photon fluorescent materials with water-solubility and permeability to cell membrane, two-photon fluorescent probes containing aldehydes will be synthesized. The aim to probe Cys and Hcy selectively may be carried out by modulating the electronic structures of fluorescent sensors containing aldehydes and addin

英文关键词： fluorescent probes；Cys/Hcy；two-photon fluorescent imaging；ultramicrostructure of organelle；high selectivity