流感病毒經由呼吸道造成嚴重的感染，導致流感疾病的大流行。在病毒感染宿主免疫系統時，病毒上的凝血素及神經胺酸水解酶，為兩個最重要抗原。近年來，禽流感的爆發以及發現對常用藥物產生抗藥性的病毒層出不窮，設計及合成神經胺酸水解酶抑制劑是一個迫切的研究方向。在本論文中，共合成約40個瑞樂沙衍生物，並針對禽流感病毒H1N1及H3N2兩種亞型進行抑制活性測試。其中，針對屬於第一基團的神經胺酸水解酶，含有疏水性的萘環基團瑞樂沙衍生物3j，展現最佳的抑制活性IC50為20 nM；在本論文中，醯基胍類的瑞樂沙衍生物對禽流感病毒H1N1及H3N2兩種亞型的抑制活性皆屬於奈米濃度。利用所延伸的醯基可與胺基酸E119及D151產生重要的氫鍵鍵結；此外，疏水性基團也可能與鄰近的活性中心-150 cavity產生作用力。在本論文的研究結果可提供幫助，發展更多具潛力的神經胺酸水解酶抑制劑。
論文的第二部分為氟標記結合化學酵素合成寡醣的研究與探討。酵素合成法適合複雜的寡醣體之合成，但在純化上有時懭時費日，且導致低產率的結果。因此，為了有效免除複雜醣體的費時費力的純化過程，綜合可行且簡單有效的純化方法是渴望的研究發展重點。為達到這目的，在本論文中，結合氟標記在醣體化合物的還原端，對於高極性的碳水化合物發展一個新穎的純化方式；成功的合成且純化得到四醣體-Sialyl Lewis X及聚N-乙醯基乳醣胺。首先，以化學合成法將氟標記掛於N-乙醯葡萄糖胺，接著利用酵素合成法，結合磷酸葡萄糖胸苷轉移酶、N-乙醯基己胺糖轉移酶、β-1,3-乙醯葡萄糖胺轉移酶、β-1,4-半乳糖轉移酶、α-1,4-半乳糖轉移酶、α-2,3-唾液酸轉移酶及α-1,3-岩藻糖轉移酶，在非還原端延伸醣鏈長度。因此，藉由氟標記，可發展多樣性的醣類分子庫。

Influenza virus is the cause of major respiratory illness in human populations, and the trimeric viral hemagglutinin (HA) and neuraminidase (NA) proteins are the two most prominent antigens targeted by the host immune system. The design and synthesis of NA inhibitors is a subject of intense research owing to both the recent outbreaks of avian influenza and the emergence of viruses that are highly resistant to widely used drugs. In this study, a series of acylguanidine-modified zanamivir analogs (~40 analogs) were synthesized, and their inhibitory activities against the NAs of avian influenza viruses (H1N1 and H3N2) were evaluated. In particular, zanamivir derivative 3j, with a hydrophobic naphthalene substituent, exhibits the best inhibitory activity against group-1 NA, with an IC50 of 20 nM. Our results show that the average IC50 values of these zanamivir derivatives are in the nanomolar range, indicating the importance of both the carbonyl group, which can generate additional contacts through hydrogen bonding with the E119 and D151 residues of NA, and the hydrophobic group, which may interact with the adjacent 150 cavity. Our results provide information that may aid in the development of more potent neuraminidase inhibitors.
Enzymatic synthesis is suitable for synthesizing complex oligosaccharides. However, tedious purification step often lead to a low overall yield and costs a lot of time. Therefore, a simple and effective method, synthetically viable to complex glycan structures circumventing the need of labor-intensive and time-consuming purification steps is highly desirable. To address this, here, we have developed a new purification technique of carbohydrates in combination with photolysis and enzymatic synthesis by incorporating a fluorous tag at the reducing end of glycans. In this study, we are successful to synthesize oligosaccharides, such as Sialyl Lewis X (SLex) and poly-LacNAc. We first synthesized the fluorous tag containing N-acetylglucosamine by chemical synthesis, and the carbohydrate chains were elongated at the non-reducing end by employing transferases, such as thymidylyltransferase (RmlA), N-acetylhexosamine-1-kinase (NahK), β-1,3-N-acetyl-glucosaminyltransferase (HpGnT), β-1,4-galactosyltransferase (NmGalT), α-1,4-galactosyltransferase (LgtC), and α-2,3-sialyltransferase (Cst I), and α-1,3-fucosyltransferas (FucT). Furthermore, we also developed a diverse glycan library through the fluorous tag.

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