請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/16905
標題: 鄰、間、對位苯雙取代氨基甲酸化合物之氨基甲酸碳-氮鍵之構型分析及其對絲胺酸水解酵素定量結構分析
Conformational Analysis and QSAR for Serine Hydrolases Esterase of the Carbamyl C-N Bond of o,m,p-Di-N-Substituted Carbamyloxy Benzenes
作者: 郭建良
Guo, Jian-Liang
關鍵字: carbamyl
氨基甲酸
出版社: 化學系所
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摘要: 本論文主要研究鄰、間、對位苯雙取代氨基甲酸化合物不同碳鏈的取代對乙醯膽鹼酯酵素、丁醯膽鹼酯酵素、脂肪酵素、膽固醇酵素等四種酵素,皆可產生抑制作用,為了瞭解抑制劑的活性(activity),應先瞭解抑制劑結構的特質,可以幫助我們瞭解抑制劑在各反應系統反應狀況的特性。使用Gaussian 09計算軟體來進行此抑制劑分子結構的幾何優化以及逐步轉動氨基甲酸C-N鍵,對抑制劑進行構形分析,探討改變碳鏈的各種抑制劑之最低能量構形、二面角、電荷和旋轉障礙能障的狀況。並將Gaussian 09理論計算出的數值與σ*、π、Es和抑制劑常數作線性迴歸,來檢視預測其相關性。 乙醯膽鹼酯酵素的pKi與最低能量呈現正相關,當能量越高其pKi值越大,故化合物a、d 、e抑制效果最佳;脂肪酵素的pKi與能量呈現負相關,當能量越低趨於穩定時,其pKi值越大,故化合物c、f、i抑制效果越佳。 BChE的pKi與其氨基甲酸上的碳之電荷成反比關係,表示當取代基的推電子效應越好時,抑制效果越佳,故化合物c、f、 i抑制效果最佳,與實驗符合。 抑制劑氨基甲酸上碳的化學位移與丁醯膽鹼酯酵素的抑制常數有高度定量線性關係;抑制劑旋轉能障與乙醯膽鹼酯酵素的抑制常數呈現負相關,當旋轉能障越低時,越容易越過狹窄溝進入活化區,抑制效果越佳。
URI: http://hdl.handle.net/11455/16905
其他識別: U0005-2506201112413700
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2506201112413700
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