結核病（Tuberculosis ，簡稱TB）是一種全球普遍性流行疾病，全球多重抗藥性結核桿菌（MDR）TB的例子日益嚴重增加，這說明需要開發一種治療結核病的新藥。參與細菌細胞壁合成α-D-葡聚醣 (α-D-glucan)成份的結核分枝桿菌麥芽糖轉移酶（Mtb GlgE）是近年來發現為結核桿菌生長的特定必需酶，適合用於設計抑制結核菌生長的目標酵素。在本論文中，我們合理設計了一系列模擬過渡態的類似物作為GlgE酶抑制劑，透過用氮原子取代醣苷 (glycosides) 的內環氧原子，將iminosugars和pseudo-醣苷上含有氮雜環官能基，作為與另一種醣苷相連的結構支架，希望藉由酶活性中心與分子所產生的電荷作用力用於抑制GlgE酶。此外，我們設計了螢光基質用於檢測GlgE酶活性指標，以磺酰氨基氧化物為螢光基團的sulfonamido-oxine-based fluorescent maltose-1-phosphates (Sox-M1P)作為主體基質，當發光團結合Mg2+，並在GlgE水解Sox-M1P後，藉由螯合增強螢光（CHEF）反應機制，以螢光強度變化達到高靈敏快速檢測的效果。另一方面，在本論文中，我們也描述了利用炔基修飾的單醣衍生物（GlcNAl，ManNAl，GalNAl和Fucyne）作為探針，藉由醣代謝生成途徑標記細菌壁中的醣共軛體 (glycoconjugates)策略。搭配一價銅離子催化疊氮-炔正交性化學反應偶合炔基官能化螢光探針的策略，希望以螢光顯影的方式檢測和區分不同菌株細胞壁表面醣共軛體，達到肉眼快速檢測的目的。

Tuberculosis (TB) is an epidemic disease and the growing burden of multidrug-resistant (MDR) TB worldwide underlines the need to develop a new drug to treat the infectious disease. Mycobacterium tuberculosis maltosyltransferase (Mtb GlgE) involved in α-D-glucan is an essential enzyme only for tuberculosis growth. We designed a series of transition-state mimic analogues as inhibitors against GlgE by replacing the endocyclic oxygen atom of glycosides with a nitrogen atom, the iminosugars and fusing membered nitrogen heterocyclic ring into the pseudo-glycoside as the structural scaffold that is linked to another glycoside for inhibiting GlgE. In addition, we designed a fluorescence dye, sulfonamido-oxine-based fluorescent maltose-1-phosphates (Sox-M1P), the chromophore binds Mg2+ and undergoes chelation-enhanced fluorescence (CHEF) upon hydrolysis of Sox-M1P by GlgE. On the other hand, we describe a metabolic oligosaccharide engineering (MOE) strategy for exploiting sugar metabolic pathways to label glycocojugates in bacteria with alkyne-modified sugar substrates (GlcNAl, ManNAl, GalNAl and Fucyne). Subsequent CuAAC [Cu(I) catalyzed Azide-Alkyne Cycloaddition] reaction with azide-functionalized probes enabled fluorescent detection and visualization of bacteria.

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