葉酸代謝對DNA/RNA的轉錄、轉譯有著巨大的影響，也因此跟各種腫瘤細胞的發展有關。葉酸代謝需透過葉酸結合蛋白來輔助。在許多惡性腫瘤組織病例中，葉酸結合蛋白的表達量與惡性腫瘤發生的機率呈現正相關。為了更清楚的研究其關係，葉酸結合蛋白的偵測及檢驗是個必備的工具。目前，發展出一種快速且具良好專一性及偵測能力的葉酸結合蛋白偵測方法依然是個大挑戰。在本論文中，我們發展出以二氟苯酯作為反應端的自解離探針用於偵測以及分析葉酸結合蛋白。此探針在與DHFR反應後最高可以產生將近180倍的螢光增益效果。在基礎生物科學研究、藥物開發以及臨床醫學診斷的領域中，我們相信此新穎的螢光探針設計將是一個可以應用在葉酸結合蛋白偵測上的重要工具。

The folate metabolisms have a great influence on the transcription, translation and repair of DNA/RNA. At present, the biological relationship between folates receptors and cancer risk remains uncertain, as various studies have demonstrated positive, negative, and neutral associations. To date, analytical method that can provide rapid, selective and sensitive detection of folate-binding proteins remains challenging to design. In this thesis, we show that fluorescent turn-on chemical probe based on a difluorophenyl hexanoate self-immolative linker can be a powerful approach to analyze folate-binding proteins in complex biological medium. The probe exhibits dramatic fluorescent enhancement of around 180-fold upon reaction with dihydrofolate reductase (DHFR). We believed that our novel probe design can be a powerful tool to analyze folate-binding proteins which is an important biological target in fundamental biological researches, drug discovery, and medical diagnosis.

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