本文選題：膽酸抗原 + 化學(xué)改性　； 參考：《內(nèi)蒙古大學(xué)》2017年碩士論文

【摘要】：膽酸是一類在哺乳類動物體內(nèi)合成的天然化合物,具有特殊的分子結(jié)構(gòu)和優(yōu)良的生物相容性。膽酸作為藥物載體最大的優(yōu)勢和特點(diǎn)是肝腸循環(huán)效率高,藥物與載體偶聯(lián)后可被運(yùn)轉(zhuǎn)蛋白識別,膽酸與載體蛋白進(jìn)行偶聯(lián)使其作為免疫原在動物體內(nèi)產(chǎn)生抗體。因此,進(jìn)一步研究膽酸化合物以及將其進(jìn)行化學(xué)改性制備出新型的膽酸抗原逐漸成為醫(yī)學(xué)上的研究熱點(diǎn)。膽酸是歷史悠久的傳統(tǒng)中藥,性味苦寒,具有良好的清熱、解毒、明目等功效,國內(nèi)外以膽汁酸為原料的藥品種類繁多,膽酸作為藥物載體的研究也越來越受到重視。本實(shí)驗(yàn)合成制備了膽酸抗原作為藥物載體,使其活化位置功能精準(zhǔn)化,從而為之后膽酸抗體注入小鼠體內(nèi)提供實(shí)驗(yàn)依據(jù)。本實(shí)驗(yàn)的主要工作是合成膽酸抗原并對其結(jié)構(gòu)進(jìn)行化學(xué)修飾使其活化位置功能精準(zhǔn)化。即與牛血清白蛋白進(jìn)行偶聯(lián),通過核磁、質(zhì)譜、高效液相色譜等表征手段確定其結(jié)構(gòu)及純度;利用SDS-PAGE(十二烷基磺酸鈉聚丙烯酰胺凝膠電泳)確定膽酸抗原是否與蛋白偶聯(lián)成功。分別在人宮頸癌細(xì)胞(HeLa)、人肺腺癌細(xì)胞(A549)、人肝癌細(xì)胞(HepG2)、人乳腺癌細(xì)胞(MAD-MB-231)上做細(xì)胞毒性實(shí)驗(yàn)以此證明生物相容性。后續(xù)需要通過基質(zhì)輔助激光解吸電離飛行時(shí)間質(zhì)譜(MALDI-TOF-MS)進(jìn)行蛋白偶聯(lián)小分子數(shù)量的確定。
[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).
【學(xué)位授予單位】：內(nèi)蒙古大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：TQ461

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