研究生: |
王泰元 Wang, Tai-Yuan |
---|---|
論文名稱: |
含氟唾液酸-石膽酸混合分子作為增強抑制癌細胞轉移能力的唾液酸轉移酶代謝抑制劑 Fluorinated sialic acid-lithocholic acid hybrid molecules as metabolic inhibitor of sialyltransferase and enhance the ability to inhibit cancer metastasis |
指導教授: |
李文山
Li, Wen-Shan 林文偉 Lin, Wen-Wei |
口試委員: |
李文山
Li, Wen-Shan 林文偉 Lin, Wen-Wei 陳焜銘 Chen, Kwun-Min |
口試日期: | 2021/07/14 |
學位類別: |
碩士 Master |
系所名稱: |
化學系 Department of Chemistry |
論文出版年: | 2021 |
畢業學年度: | 109 |
語文別: | 英文 |
論文頁數: | 153 |
中文關鍵詞: | 唾液酸 、唾液酸轉移酶 、石膽酸 、唾液酸轉移酶代謝抑制劑 、癌症轉移 |
英文關鍵詞: | Sialic acid, Sialyltransferase, Lithocholic acid, Sialyltransferase metabolic inhibitor, Cancer metastasis |
研究方法: | 實驗設計法 、 行動研究法 、 準實驗設計法 |
DOI URL: | http://doi.org/10.6345/NTNU202100933 |
論文種類: | 學術論文 |
相關次數: | 點閱:140 下載:0 |
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含氟唾液酸可以抑制唾液酸轉移酶的活性,以調節唾液酸的生物合成及其補救途徑,加上石膽酸本身也表現出對唾液酸轉移酶的顯著抑制特性。在本篇論文中,我們合成了一系列具有糖苷酯鍵和酯鍵連接的含氟唾液酸-石膽酸混合分子。希望它們可以與唾液酸轉移酶相互作用並協同調控唾液酸的生物合成,以抑制細胞表面唾液酸化的發生。
最後,我們合成了一系列混合分子TYW01-TYW12,並進行了初步的生物試驗。令人驚訝的是,TYW01-TYW12對唾液酸轉移酶沒有抑制作用,但對人類三陰性乳癌細胞株MDA-MB-231有輕微的抗轉移作用。其中,TYW10的影響較為顯著,IC50範圍為40 µM至50 µM。需要更進一步的生物實驗和研究來證實這些結果。
Sialyltransferases (STs) activity can be inhibited using a fluorinated sialic acid (3FaxNeu5Ac) to affect/regulate both the de novo synthesis of sialic acid and its salvage pathway. In addition, lithocholic acid (LCA) itself also demonstrated potent inhibitory property toward STs. In this work, we synthesized a series of P-3FaxNeu5Ac-GA-LCA (GA, Glycolic acid) hybrid molecules with glycosidic ester bonds linkage. Hopefully, they can interact with STs and manipulate the biosynthesis of sialic acid synergistically to inhibit/modulate the occurrence of sialylation on cell surface.
Finally, we synthesized a series of hybrid molecules TYW01-TYW12 and tested their preliminary biological experiments. Surprisingly, TYW01-TYW12 showed no inhibitory effect toward sialyltransferase, but mild anti-migration effect in MDA-MB-231 cell. Among them, TYW10 has the best effect with IC50 ranging from 40 µM to 50 µM. Further biological experiments and studies are needed to confirm these results.
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