腫瘤相關抗原Globo-H與SSEA-3之合成研究

Toward the Synthesis of Tumor-Associated Antigens Globo-H and SSEA-3

陳仲宇(Chung-Yu Chen)

指導教授 ： 林俊成

國立清華大學/理學院/化學系/碩士(2009年)

https://doi.org/10.6843/NTHU.2009.00320

摘要

Globo-H六醣體為乳癌細胞表面大量表達的碳水化合物抗原，目前已成為開發乳癌疫苗的熱門目標。近年研究發現，Globo-H缺乏岩藻糖之五醣體前趨物—SSEA-3於乳癌幹細胞上的表現量較Globo-H高，因此亦逐漸成為另一個乳癌疫苗的開發標的。
本論文之目的在於Globo-H與SSEA-3的合成方法研究。於合成策略上，以一鍋化醣基化反應為目標，希望利用已知的方法，設計適合的建構單元，以期能應用在兩種醣體的合成。在α-D-Gal-(1→4)-β-D-Gal-(1→4)-β-D-Glc三醣體合成中，乳糖受體以芐基保護時可得到醣苷鍵完全為α位向之產物，不會產生β位向之產物。合成β-D-Gal-(1→3)-β-D-GalNAc雙醣片段時，半乳糖胺受體以價格低廉之半乳糖為起始物，C-2位置製備成疊氮基，而半乳糖予體之C-2位置選用苯甲醯基保護時可控制醣苷鍵為β位向，此雙醣體亦嘗試改用苯甲醯基與Troc保護之受體提升醣基化反應之效率。我們使用合成出的雙醣與三醣片段，完成五醣體的合成。於本論文之合成策略中，進行醣基化反應時，醣苷鍵之α、β位向皆有良好的選擇性，為此類醣體之合成提供一有效而方便的路徑。

關鍵字

醣基化反應

並列摘要

Globo-H hexasaccharide is a tumor-associated carbohydrate antigen that is highly expressed on the surface of breast cancer cells. This hexasaccharide has been aimed at development of anti-breast cancer vaccine. In recent study, the pentasaccharide precursor of Globo-H, SSEA-3, was found that its expression in breast cancer stem cells was higher than Globo-H. As a result, SSEA-3 has become another candidate for anti-breast cancer vaccine.
In this thesis we focus on the synthetic methods of Globo-H and SSEA-3. Our strategy is base on one-pot glycosylation method and we want synthesize these two oligosaccharides by using well-know protocols. In the synthesis of α-D-Gal-(1→4)-β-D-Gal-(1→4)-β-D-Glc trisaccharide, we can get exclusive α product by using benzyl-protected lactose acceptor, and no β isomer was observed. In the synthesis of β-D-Gal-(1→3)-β-D-GalNAc disaccharide, we use cheap and commercial available galactose as starting material of GalNAc acceptor, and we used azide group at C-2 position. The exclusive β disaccharide can be synthesized by using benzoyl group at C-2 position of galactose donor. We use the benzoyl- and Troc-protected GalNAc acceptor to improve the efficiency of glycosylation. The pentasaccharide compound has been synthesized by using our building blocks. In this thesis, the α/β selectivity is good in every glycosylation reaction. We established a simple and efficient pathway to achieve the synthesis of this oligosaccharide.

並列關鍵字

Globo-H ； SSEA-3

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