https://scholars.lib.ntu.edu.tw/handle/123456789/177251
標題: | 設計及合成SARS冠狀病毒蛋白酶抑制劑:建構a-羥基膦酸二烷基酯、a-羥基醯胺與a-酮基醯胺之小型分子庫 Design and Synthesis of SARS-CoV Protease Inhibitors: Small Libraries of a-Hydroxy Diethyl Phosphonate, a-Hydroxy Amide and a-Keto Amide |
作者: | 黃鴻鈞 Huang, Hung-Jyun |
關鍵字: | 蛋白酶;抑制劑;羥基膦酸二乙基酯;酮基醯胺;嚴重急性呼吸道症候群;羥基醯胺;hydroxy diethyl phosphonate;hydroxy amide;Severe Acute Respiratory Syndrome;keto amide;SARS;protease inhibitors | 公開日期: | 2004 | 摘要: | SARS,是Severe Acute Respiratory Syndrome的縮寫,中文稱之為嚴重急性呼吸道症候群,引起此疾病的主要元凶是SARS冠狀病毒。我們在本論文中報導了SARS冠狀病毒主要蛋白酶抑制劑開發的方法,同時模擬病毒蛋白酶活性中心四面體結構的特性,利用a-羥基膦酸二乙基酯(i)、a-羥基醯胺(ii)以及a-酮基醯胺(iii)等基本架構配合組合式化學方法來建立小型分子庫,並且使用螢光分析法進行主要蛋白酶活性抑制測試。 目前已從數百種化合物當中找尋到約二十種抑制效用在10 uM以下的化合物,而抑制效用低於1 uM的化合物亦有兩種被開發出來。利用我們建構出來的分子庫,去篩選對於病毒主要蛋白酶具有良好抑制效果的前導性化合物做為未來開發治療SARS的藥物。 Severe Acute Respiratory Syndrome (SARS) is caused by infection with a novel human coronavirus (SARS-CoV). We report herein the method developed to inhibit the main protease of SARS coronavirus. We used the core structure of a-hydroxy diethyl phosphonate(i),a-hydroxy amide(ii) and a-keto amide(iii), respectively, to mimic the tetrahedral transition state of the main protease. Small libraries of protease inhibitors were constructed by using combinatorial chemistry, and some molecules having potent inhibition ability against SARS-CoV 3CLpro were discovered. More than 20 compounds out of hundreds test samples were shown to have inhibition activities at concentrations <10 uM, and two compounds have inhibition activities at <1 uM. We hope these lead compounds can be developed in future to become therapeutical agents of SARS. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/51660 | 其他識別: | zh-TW |
顯示於: | 化學系 |
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ntu-93-R90223006-1.pdf | 23.31 kB | Adobe PDF | 檢視/開啟 |
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