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研究生： 徐子凡
Hsu, Zih-Fan
論文名稱： 探討雙高石膽酸衍生物對於唾液酸轉移酶及癌細胞轉移的影響
Bishomolithocholic Acid: A Unique Template for Human Sialyltransferase Inhibitor, Optimized to Suppress Cancer Metastasis
指導教授： 李文山
Li, Wen-Shan
林文偉
Lin, Wen-Wei
學位類別： 碩士
Master
系所名稱： 化學系
Department of Chemistry
論文出版年： 2019
畢業學年度： 107
語文別： 英文
論文頁數： 96
中文關鍵詞： 唾液酸 、唾液酸轉移酶 、癌症轉移 、雙高石膽酸
英文關鍵詞： sialic acid, sialyltransferase, metastasis, bishomolithocholic acid
DOI URL： http://doi.org/10.6345/NTNU201900320
論文種類： 學術論文
相關次數： 點閱：103  下載：0 
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    • 中文摘要 I Abstract II 謝誌 III Contents IV Scheme Contents VII Table Contents VIII Figure Contents IX List of Abbreviation X Awards & Honors XII I. Introduction 1 1.1. Background 1 1.2. Sialic Acid 2 1.3. Sialyltransferase 4 1.4. Sialylated Antigen 7 1.4.1 Sialyl Lewis antigens (SLea and SLex) 7 1.4.2 Truncated O-glycans 8 1.4.3 Highly branched N-glycan 8 1.4.4 Polysialic acid (polySia) 8 1.4.5 Glycosphingolipid (GSL) 9 1.5. Sialylation in Cancer Metastasis 9 1.5.1 Metastatic process 9 1.5.2 Role of glycoconjugates in metastasis 10 1.6. Sialyltransferase Inhibitors 12 1.6.1 Donor analogous inhibitors 12 1.6.2 Transition-state analogous inhibitors 13 1.6.3 Acceptor analogous inhibitors 13 1.6.4 Other sialyltransferase inhibitors 14 1.7. Previous Study 15 1.8. Research Motivation 19 II. Results and Discussion 21 2.1. Synthesis of Bishomolithocholic Acid Derivatives HZF01-04 21 2.1.1. Retrosynthesis 21 2.1.2. Synthesis of PEG linker 1a-1d 22 2.1.3. Synthesis of bishomolithocholic diacid 10 23 2.1.4. Synthesis of bishomolithocholic acid derivatives 25 2.2. In Vitro Studies of HZF01-04 27 2.2.1. Cytotoxicity of HZF01-04 in MDA-MB-231 27 2.2.2. Inhibition of ST3Gal I and ST6Gal I 28 2.2.3. Antimigration activity of HZF01-04 29 2.2.4. Cytotoxicity of HZF01-04 in MDA-MB-231 (SFM) 32 2.3. Preliminary Structure-Activity Relationship Studies 33 III. Conclusions 37 IV. Material and Methods 39 4.1. General Experimental 39 4.2. Synthetic Procedures 40 4.2.1. Preparation of PEG linker 40 4.2.2. Preparation of bishomolithocholic acid 43 4.2.3. Preparation of HZF01 46 4.2.4. Preparation of HZF02 49 4.2.5. Preparation of HZF03 52 4.2.6. Preparation of HZF04 55 4.3. Cell Line Used and Cell Culture 58 4.4. MTT Cytotoxicity Analysis 58 4.5. Sialyltransferase Assay 58 4.6. Transwell Migration Assay 59 V. References 61 Spectra 69

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