1. 立體化學與藥物活性探討：類石膽酸衍生物與唾液酸轉移酶抑制劑 2. 藥物-生物素的結合與免疫沉澱應用

• Main Author: 鍾鎮宇
• Other Authors: 李文山
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/61162687050491561820

碩士 === 國立臺灣師範大學 === 化學系 === 99 === Part I: Impact of stereochemistry in biological properties of sialyltransferase (ST) inhibitors: Iso-lithocholic acid analogues Lithocholic acid analogues, a series of sialyltransferase inhibitors, are later confirmed by our laboratory to suppress cancer metastasis in breast cancer cells and lung cancer cells in vitro and in vivo. Here, reversal of stereochemistry of hydroxyl group in C3 position of lithocholic acid, iso-lithocholic acid, is developed and synthesized. Biological evaluation of iso-lithocholic acid and its analogues (3、11、17、20、23、25、27) show that most of them effectively suppress metastasis of breast cancer cell using wound healing assay. Especially, compound 25 and 27 show ability of inhibiting α-2,6(N)-ST activity by the method of HPLC assay, developed in our laboratory previously. In summary, iso-lithocholic acid analogues with opposite stereochemistry (versus lithocholic acid) exhibit important therapeutic values relating not only to inhibitory manner of ST but also to anti-metastatic behaviors of cancer cell lines. Part II: Biotin-conjugated anticancer agents and their applications in immunoprecipitation In cell biology, utilization of high affinity between streptavidin and biotin is commonly used in protein targeting, purification and enhancement. We modify and prepare anticancer agents, SK228 and NBD-Asp-LA, by conjugation with biotin and use them to identify and recognize their biological partners, the proteins. Due to the reduction of antiproliferative activity of biotin-conjugated SK228, we cannot detect any proteins after immunoprecipitation assay. On the other hand, biotin-conjugated NBD-Asp-LA shows the effective inhibition potency against sialyltransferase and its application to catch biological target protein will be evaluated later using immunoprecipitation assay.