定量結構分析短鏈型硫代氨基甲酸類化合物抑制青黴素酶及凝血酶

龔郁潔

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定量結構分析短鏈型硫代氨基甲酸類化合物抑制青黴素酶及凝血酶

QSAR for Inhibition of Penicillinase and Thrombin by Short-chain Thiocarbamates

龔郁潔 , Masters　　Advisor：林家立　　

繁體中文

定量結構分析；硫代氨基甲酸類化合物；青黴素酶凝血； QSAR ； Short-chain Thiocarbamates ； Penicillinase ； Thrombin

Abstract │ Reference (43) │ Times Cited (5) │ Altmetrics

Abstract 〈TOP〉

本論文主要研究的是短鏈型硫代氨基甲酸類化合物，3-N-(ethyl、n-propyl、n-butyl、t-butyl、benzyl)thiocarbamyl propanol(1–5)及1,3-di-N-(ethyl、n-propyl、n-butyl、t-butyl、benzyl)thiocarbamyl propane (6–10)為青黴素酶和凝血酶的抑制劑。由停時驗析得知抑制劑1–10皆屬類受質抑制劑。透過非線性迴歸得到解離常數(Ki)、反應速率常數(k2)及總抑制常數(ki)。抑制劑1–10比青黴素抑制劑sulbactam及凝血酶抑制劑coumadin的抑制效果好。  在QSAR研究方面，將抑制劑1–10抑制兩種酵素的動力學常數(Ki、k2、ki)  之對數值，與取代基常數、疏水性常數及立體效應常數作單一及多參數線性迴歸，發現均有良好線性關係。抑制劑1-5抑制青黴素酶的pKi與抑制劑1-5取代基常數σ*間有良好線性關係，ρ* = 6±1；抑制劑6-10抑制青黴素酶的pKi與抑制劑6-10取代基常數σ*間有良好線性關係，ρ* = 2.6±0.2。因ρ* >0，所以Ki步反應經由帶負電之過渡狀態，形成帶負電之四面體中間產物。疏水性常數的斜率ψ值和立體效應的斜率δ值相較於取代基常數的斜率ρ*值較小，表示對於此抑制反應之K୧步而言，取代基的電子效應的影響大過於取代基的疏水性及取代基的立體效應。抑制劑1-5抑制青黴素酶的logk2與抑制劑1-5取代基常數σ*間有良好線性關係，ρ* = -1.2±0.4；抑制劑6-10抑制青黴素酶的logk2與抑制劑6-10取代基常數σ*間有良好線性關係，ρ* = -0.22±0.05。因ρ* <0，所以k2步反應經由帶正電之過渡狀態，形成帶正電之中間產物。疏水性常數的斜率ψ值和立體效應的斜率δ值相較於取代基常數的斜率ρ*值較小，表示對於此抑制反應之k2步而言，取代基的電子效應的影響大過於取代基的疏水性及取代基的立體效應。而青黴素酶ρ*值相當大，因此推測青黴素酶的陰離子洞有三個氨基酸的NH所形成的氫鍵。  抑制劑1-5抑制凝血酶的pKi與抑制劑1-5取代基常數σ*間有良好線性關係，ρ* =1.3±0.3；抑制劑6-10抑制凝血酶的pKi與抑制劑6-10取代基常數σ*間有良好線性關係，ρ* = 1.0±0.4。因ρ* >0，所以Ki步反應經由帶負電之過渡狀態，形成帶負電之四面體中間產物。疏水性常數的斜率ψ值和立體效應的斜率δ值相較於取代基常數的斜率ρ*值較小，表示對於此抑制反應之K୧步而言，取代基的電子效應的影響大過於取代基的疏水性及取代基的立體效應。抑制劑1-5抑制凝血酶的logk2與抑制劑1-5取代基常數σ*間有良好線性關係，ρ* = -0.16±0.03；抑制劑6-10抑制凝血酶的logk2與抑制劑6-10取代基常數σ*間有良好線性關係，ρ* = -0.14±0.02。因ρ* <0，所以k2步反應經由帶正電之過渡狀態，形成帶正電之中間產物。疏水性常數的斜率ψ值和立體效應的斜率δ值相較於取代基常數的斜率ρ*值較小，表示對於此抑制反應之k2步而言，取代基的電子效應的影響大過於取代基的疏水性及取代基的立體效應。而凝血酶的ρ*值略小，推測其陰離子洞有兩個氨基酸的NH所形成的氫鍵。  抑制劑1–3，5–8及10的硫代氨基甲酸的碳有兩種13C化學位移，而抑制劑4和9只有一個。經理論計算後，推測抑制劑1–3及5有類順式(pseudo cis)及類反式(pseudo trans)兩種構形，6–8及10有類順–順式(pseudo cis-cis)、類順–反式(pseudo cis-trans)兩種構形。抑制劑4只有類反式構形，抑制劑9只有類順-順式構形。將抑制劑1–5硫代氨基甲酸類化合物的碳之13C化學位移δ1與取代基常數作線性迴歸，有良好線性關係。 抑制劑1–5硫代氨基甲酸類化合物的碳之13C化學位移與其理論計算之電荷作線性迴歸，也有良好線性關係。

Reference ( 43 ) 〈TOP〉

1.E. J. Lietz, H. Truher , D. Kahn, M. J. Hokenson, A. L. Fink, Lysine-73 is involved in the acylation and deacylation of beta- lactamase, Biochemistry, 2000, 39, 4971-4981.
連結：
2.J. D. Hayes, C. R.Wolf, Molecular mechanisms of drug resistance. Biochem. J., 1990 , 272, 281-295.
連結：
3.C. Oefner, A. D'Arcy, J. J. Daly, K. Gubernator, R. L. Charnas, I. Heinze, C. Hubschwerlen, Winkler FK. Refined crystal structure of beta-lactamase from Citrobacter freundii indicates a mechanism for beta-lactam hydrolysis, Nature, 1990 , 343, 284-288.
連結：
4.D. L. Nelson, M. M. Cox ,Lehninger principles of biochemistry, 4th ed., New York: WH Freeman and Company, 2005, pp. 779-780.
連結：
5.Wing Y. Tsang, Naveed Ahmed, Paul S. Hinchliffe, J. Matthew Wood, Lindsay P. Harding, Andrew P. Laws, and Michael I. Page, Different Transition-State Structures for the Reaction of β-Lactams and Analogous β-Sultams with Serine β-lactamase,J.AM.CHEM.SOC., 2005, 127,17556-17564.
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Times Cited (5) 〈TOP〉

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