Globo-系列醣體被認為與癌症的演進有很高的關聯性。這些醣體之中，DSGb5被發現大量表達於腎細胞癌 (RCC) 且與 RCC 的轉移有關；而在乳癌細胞表面則大量表現 Gb5、SSEA4以及 Globo H。除外，唾液酸常被發現存在於細胞表面醣體的末端。唾液酸免疫球蛋白凝集素 (Siglecs) 藉由辨識病原體表面的唾液酸來調節免疫細胞功能的運作，癌細胞藉此躲過生理上的免疫防禦機制。Siglecs 被認為是治療免疫相關疾病的明日之星。因此，找尋不同唾液酸鍵結的唾液酸苷以及評估其與 Siglecs 間的親和力相當重要。
本論文利用多種酵素來建構 Globo-系列醣體，包含 Gb3、Gb4、Gb5 及 Globo H，並利用不同來源的唾液酸轉移酶催化上述醣體進行唾液酸化反應，生成 Globo-系列唾液酸苷。除外，亦利用酵素方法成功合成 DSGb5。同時也發現利用不同來源的 -2,6-唾液酸轉移酶 (PdST 及 PspST) 催化 SSEA4進行反應會得到不同的產物。接著，利用醣微矩陣技術來分析 Siglec-7與雙唾液酸化 Globo-系列醣體之間的親和力。實驗發現不具脂鏈的 DSGb5與 Siglec-7的結合力很弱。推測 DSGb5與 Siglec-7的親和力作用可能與脂鏈有關聯。

It is known that globo series of gangliosides are strongly associated with some cancers. Among these glycans, DSGb5 was from renal cell carcinoma (RCC) and was thought to be correlated with RCC metastases while Gb5, SSEA4 and Globo H were overexpressed on breast cancer cells. In addition, sialic acids are usually found at the terminal residue of glycans on the cell surface glycoproteins and glycolipids. Sialic acid-binding Ig-like lectins (Siglecs) regulate the immune cell functions by specifically recognize different sialic acid ligands on the cell surface of pathogens. For example, DSGb5, a preferred ligand for Siglec-7 inhibits the cytotoxicity of NK cells. Siglecs have been considered to be promising theraputic candidates for immune-cell-mediated diseases. Therefore, discovery of new sialosides and evaluation of their binding specificity and affinity with Siglecs are crucial.
In this thesis, we conducted a small library of carbohydrate-active enzymes to construct various globo-series glycans, including Gb3, Gb4, Gb5, and Globo H. The Gb3, Gb4 and Gb5 were further sialylated by different sialyltransferases to yield globo-series sialosides. We have successfully synthesized DSGb5 by enzymatic synthesis. It’s interesting to find that -2,6-sialylation of SSEA4 by different -2,6-sialyltransferases (PdST and PspST) gave different products. The glycan microarray was used to evaluate the binding affinity between Siglec-7 and disialylated Globo-series glycans. It’s surprising to find that DSGb5 without lipid chain only show low binding affinity to Siglec-7, indicating that the lipid chain of glycan might play an important role in Siglecs binding.

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