谷胱甘肽荧光探针的合成及性质研究

发布时间：2018-05-02 12:02

本文选题：谷胱甘肽 + 荧光探针　；参考：《华中师范大学》2016年硕士论文

【摘要】：谷胱甘肽是生物体内重要的活性物质,具有许多生理功能。研究已表明谷胱甘肽可用于体内氟化物、丙烯腈、重金属及有机溶剂等的中毒治疗；保护细胞膜免受氧化性破坏；促进高铁血红蛋白的还原；保护由肿瘤药物、放射性药物等引起的白细胞减少症状；缓解由缺氧血症、恶心以及肝脏疾病所引起的不适等功能。然而体内谷胱甘肽含量过高或过低都会影响正常的生理机能,导致一些疾病的产生如肝损伤、癌症、艾滋病、骨质疏松症、阿耳茨海默氏病、心血管疾病等,所以维持体内谷胱甘肽含量的稳定是非常重要的。由于半胱氨酸、同型半胱氨酸与谷胱甘肽具有相似的分子骨架和反应活性(如巯基),导致在细胞内高选择性的检测谷胱甘肽相当困难。因此,如何快速、高效、准确和专一性地检测细胞内谷胱甘肽具有很大的挑战。本论文设计并合成了三类谷胱甘肽荧光探针。具体工作内容如下：1.设计并合成了以丹磺酰胺为荧光团的铜离子／谷胱甘肽荧光探针。实验结果表明,该探针能够高选择性地识别铜离子并不受其它金属离子的干扰,此外生成的铜离子配合物可进一步用于谷胱甘肽的检测。2.设计并合成了以七甲川菁染料为骨架的谷胱甘肽荧光探针。实验结果表明,该探针在生理条件下展现了对谷胱甘肽的高选择性并不受其它氨基酸的干扰。细胞实验表明,该探针适用于细胞内检测谷胱甘肽,并可区分半胱氨酸和同型半胱氨酸。老鼠成像表明,该探针可运用于老鼠体内检测谷胱甘肽并且产物可以进一步代谢排出。3.设计并合成了以1,8-萘酰亚胺磺酰胺为骨架的谷胱甘肽荧光探针。荧光光谱数据表明,该探针在生理条件下能够高选择性地识别谷胱甘肽并区分半胱氨酸和同型半胱氨酸。细胞成像表明,探针可适用于细胞内专一性检测谷胱甘肽,并定位于亚细胞溶酶体内检测谷胱甘肽。
[Abstract]:Glutathione is an important active substance in organism and has many physiological functions. Studies have shown that glutathione can be used to treat fluoride, acrylonitrile, heavy metals and organic solvents in vivo; to protect cell membranes from oxidative damage; to promote methemoglobin reduction; and to protect against cancer drugs. Leucopenia caused by radiopharmaceuticals; relief from anoxia, nausea, and malaise caused by liver disease. However, high or low levels of glutathione in the body can affect normal physiological function, leading to some diseases such as liver injury, cancer, AIDS, osteoporosis, Alzheimer's disease, cardiovascular disease, etc. Therefore, it is very important to maintain the stability of glutathione content in the body. Because of cysteine, homocysteine and glutathione have similar molecular skeleton and reactive activity (such as thiol), which makes it very difficult to detect glutathione in cells with high selectivity. Therefore, how to detect intracellular glutathione quickly, efficiently, accurately and specifically is a challenge. In this paper, three kinds of glutathione fluorescent probes were designed and synthesized. The details of the work are as follows: 1. Copper ion / glutathione fluorescent probe with dansulfonamide as fluorescence group was designed and synthesized. The experimental results show that the probe can highly selectively recognize copper ions without interference from other metal ions, and the resulting copper ion complexes can be further used for the detection of glutathione. 2. A glutathione fluorescence probe with heptomethylcyanine dyes as skeleton was designed and synthesized. The results showed that the probe exhibited high selectivity to glutathione under physiological conditions without interference by other amino acids. Cell experiments showed that the probe was suitable for intracellular detection of glutathione and could distinguish cysteine from homocysteine. Mouse imaging showed that the probe could be used to detect glutathione in mice and that the product could be metabolized further. A glutathione fluorescence probe was designed and synthesized with 1 D 8 naphthalimide sulfonamide as the skeleton. Fluorescence spectra showed that the probe could selectively recognize glutathione and distinguish cysteine from homocysteine under physiological conditions. Cell imaging showed that the probe could be used to detect glutathione specifically in cells and to detect glutathione in subcellular lysosomes.
【学位授予单位】：华中师范大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O657.3

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