胆酸类化合物的化学改性及其抗原的制备和表征

发布时间：2018-05-11 02:30

本文选题：胆酸抗原 + 化学改性　；参考：《内蒙古大学》2017年硕士论文

【摘要】：胆酸是一类在哺乳类动物体内合成的天然化合物,具有特殊的分子结构和优良的生物相容性。胆酸作为药物载体最大的优势和特点是肝肠循环效率高,药物与载体偶联后可被运转蛋白识别,胆酸与载体蛋白进行偶联使其作为免疫原在动物体内产生抗体。因此,进一步研究胆酸化合物以及将其进行化学改性制备出新型的胆酸抗原逐渐成为医学上的研究热点。胆酸是历史悠久的传统中药,性味苦寒,具有良好的清热、解毒、明目等功效,国内外以胆汁酸为原料的药品种类繁多,胆酸作为药物载体的研究也越来越受到重视。本实验合成制备了胆酸抗原作为药物载体,使其活化位置功能精准化,从而为之后胆酸抗体注入小鼠体内提供实验依据。本实验的主要工作是合成胆酸抗原并对其结构进行化学修饰使其活化位置功能精准化。即与牛血清白蛋白进行偶联,通过核磁、质谱、高效液相色谱等表征手段确定其结构及纯度;利用SDS-PAGE(十二烷基磺酸钠聚丙烯酰胺凝胶电泳)确定胆酸抗原是否与蛋白偶联成功。分别在人宫颈癌细胞(HeLa)、人肺腺癌细胞(A549)、人肝癌细胞(HepG2)、人乳腺癌细胞(MAD-MB-231)上做细胞毒性实验以此证明生物相容性。后续需要通过基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)进行蛋白偶联小分子数量的确定。
[Abstract]:Cholic acid is a kind of natural compounds synthesized in mammals. It has special molecular structure and excellent biocompatibility. The greatest advantage and characteristic of cholic acid as drug carrier is that the efficiency of liver and intestine circulation is high. The conjugation of cholic acid with carrier protein can be recognized by the transporter protein, and the conjugation of cholic acid with carrier protein makes it produce antibody in animal body as immunogen. Therefore, the further study of cholic acid compounds and the preparation of new cholic acid antigens by chemical modification have gradually become the focus of medical research. Cholic acid is a kind of traditional Chinese medicine with a long history. It has a good effect of clearing away heat, detoxifying and eyesight. There are many kinds of drugs with bile acid as raw material at home and abroad, and the study of cholic acid as drug carrier has been paid more and more attention. In this experiment, cholic acid antigen was synthesized as drug carrier, and its activation position function was precise, which provided experimental basis for later injection of cholic acid antibody into mice. The main work of this experiment is to synthesize cholic acid antigen and modify its structure chemically to make the function of activation position accurate. The structure and purity of bovine serum albumin were determined by NMR, mass spectrometry and high performance liquid chromatography, and the conjugation of cholic acid antigen with protein was determined by SDS-PAGE (sodium dodecyl sulfonate polyacrylamide gel electrophoresis). Cytotoxicity tests were performed on human cervical cancer cell line, human lung adenocarcinoma cell line A549, human hepatocellular carcinoma cell line HepG2, human breast cancer cell line MAD-MB-231) to prove biocompatibility. It is necessary to determine the number of protein-coupled small molecules by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS).
【学位授予单位】：内蒙古大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ461

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