唾液酸轉移酶（Sialyltransferases, STs）可被含氟唾液酸（Sia3Fax）抑制， 進而影響唾液酸的 de novo 合成與修復路徑（salvage pathway）。石膽酸 （Lithocholic acid, LCA）也與 Sia3Fax 類似，展現出顯著的 ST 抑制活性。 我們先前合成了含有醣苷鍵與酯鍵連結的 Sia3Fax–LCA 混和分子，並意外 發現其中 TYW 系列化合物在酵素測定中能增強 ST6Gal I 活性。這是首 次有關 ST 活化劑的研究，此一發現激起我們進一步探究的興趣。 本研究中，我們將 LCA 與唾液酸間的酯鍵修飾為更不易水解的醯胺 鍵，成功合成出 ALL01 至 ALL06 系列化合物；值得注意的是，在 20 M （低於其在 M10 細胞中的 IC50 值）濃度下，ALL01（IC50 = 38.02 M） 與 ALL02（IC50 = 77.56 M）分別促進 ST 活性達 282% 與 270%；在 HEK293 細胞內免疫螢光分析，結果顯示ALL02顯著提高了細胞表面唾液 酸化程度，相較於對照組增加約1.3倍，表明ALL02是最有前景的活化劑。 我們期望透過 ALL01及ALL02 增強 ST 活性，進而調節 B 細胞抗體的 產生，以改善免疫功能缺陷相關問題。;Sialyltransferases (STs) can be inhibited by fluorinated sialic acid (Sia3Fax), affecting sialic acid de novo synthesis and salvage pathways. Lithocholic acid (LCA) also exhibits significant ST inhibition, as Sia3Fax does. Previously, we synthesized Sia3Fax-LCA hybrids with glycosidic and ester linkages, unexpectedly finding that the TYW series enhanced ST6Gal I activity in ST assays. This is the first report for the STs activator. The discovery sparked curiosity and prompted further research. In this study, we replaced the ester bond between LCA and sialic acid with an amide bond, which is more resistant to hydrolysis, synthesizing ALL01─ALL06. Notably, at a concentration of 20 M (below their respective IC50 values in M10 cells), ALL01 (IC50 = 38.02 M) and ALL02 (IC50 = 77.56 M) enhanced ST activity by 282% and 270%, respectively. Intracellular immunofluorescence analysis of HEK293 cells treated with equal concentrations of ALL01 and ALL02 showed that ALL02 significantly increased cell surface sialylation by 1.3-fold compared to the control, suggesting ALL02 as the most promising activator. We aim to enhance ST activity through ALL01 and ALL02 to modulate B cell antibody production, thereby addressing immune function deficiencies.
