Synthetic Route of Heptaprenol Derivative for Developing FRET Based Assay to Screen Glycosyltransferase Inhibitors
Date Issued
2007
Date
2007
Author(s)
Yang, Yi-Hsun
DOI
en-US
Abstract
細菌對抗生素所產生的抗藥性從數十年前就不斷的增加, 但在此期間所對應的抗生素並沒有隨著抗藥性的增加而以相同的速度被發現並且應用在臨床上. 目前所使用的抗生素不是在數十年前就被發現並使用就是以現有的抗生素的結構為骨架而做修飾而來.
新藥引入的緩慢有部份是歸因於目前沒有一個有效的藥物篩選方法. 因此我們嘗試建構一個以螢光共振能量傳遞為原理的新的藥物篩選方法. 我們設計了以Lipid II為骨架的類似物並且在它的兩端加上螢光團. 兩個螢光團分別修飾在(L)賴氨酸的支鏈氨基上和萜;烯長碳鏈的末端. Lipid II的長碳鏈的長度是可以經由化學合成調整長度, 並且可以藉由調整長度來達到能量轉移效率的最佳化.
經由這樣的設計我們希望能夠建立一個能夠快速篩選醣基轉移酶;抑制劑的方法. 以楓基為輔助基來幫助達成的丙烯基和丙烯基的耦合反應被引用在合成路徑裡. 這幫助將來可以合成更多不同長度的長碳鏈萜;烯類並應用在這樣的篩選檢測裡.
Bacterial drug resistance increased in decades. There are few drugs which were introduced clinically due to the lack of an efficient screen method. Therefore we attempt to develop a new assay detecting compound inhibitory property to GTase (glycosyltransferase) based on FRET (Fluorescence Resonance Energy Transfer). We have designed a Lipid II analogue with two fluorophores on two terminal of lipid II. The length of the lipid chain is tunable in order to find a proper length for our purpose. In this way, we want to develop a HPT (high throughput) assay to detect GTase inhibitors. Sulfonyl group assisted allyl-allyl coupling has been applied to the convenient and convergent synthetic route. It helps us to further synthesize tunable length of linear terpene chain for the screen assay.
Subjects
合成
七異戊醇衍生物
synthesis
heptaprenol derivative
Type
thesis
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