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

34.204.186.91，Hello！

Close
Search Quick Search Advanced Search Publication Search	Personal Service Member Login Searching History Use Bonus Card SYMSKAN
Browse Browse by University of Graduate Thesis Browse by Pinyin of Graduate Thesis Browse by Conference Proceedings Topic Browse by Conference Proceedings Publisher Browse by Pinyin of Conference Proceedings Browse by eBook Category Browse by eBook Topic Browse by eBook Publisher
Customer Services Authorize Airiti Recommend a Journal

Search Symbol (Half-width)	Description of Search Symbols
Space	"AND" indicates the intertwining of key terms used in a search
Double Quotation Marks ("") ( " " )	Double quotation marks indicate the beginning and end of a phrase, and the search will only include terms that appear in the same order of those within the quotations. Example: "image process" ： " image process "
?	Indicates a variable letter. Entering two ? will indicate two variable letters, and so on. Example: "Appl?", search results will yield apple, apply… e , appl y … ( (often used to English word searches) )
*	Indicates an unlimited number of variable letters to follow, from 1~n. Example: Enter "appl*", search results will yield apple, apples, apply, applied, application…(often used in English word searches) e , appl es , appl y , appl ied , appl ication … ( (often used to English word searches) )
AND、OR、NOT	Boolean logic combinations of key words is a skill used to expand or refine search parameters. (1) AND (1) AND: Refines search parameters (2) OR (2) OR: Expands search parameters (3) NOT: Excludes irrelevant parameters

DOI stands for Digital Object Identifier （ D igital O bject I dentifier ） ,
and is the unique identifier for objects on the internet. It can be used to create persistent link and to cite articles.

Using DOI as a persistent link

To create a persistent link, add「http://dx.doi.org/」「 http://dx.doi.org/ 」 before a DOI.
For instance, if the DOI of an article is 10.5297/ser.1201.002 , you can link persistently to the article by entering the following link in your browser: http://dx.doi.org/ 10.5297/ser.1201.002 。
The DOI link will always direct you to the most updated article page no matter how the publisher changes the document's position, avoiding errors when engaging in important research.

Cite a document with DOI

When citing references, you should also cite the DOI if the article has one. If your citation guideline does not include DOIs, you may cite the DOI link.

DOIs allow accurate citations, improve academic contents connections, and allow users to gain better experience across different platforms. Currently, there are more than 70 million DOIs registered for academic contents. If you want to understand more about DOI, please visit airiti DOI Registration （ doi.airiti.com ）。

Data Source

Basic & Applied Sciences > Chemistry
College of Science > Department of Chemistry

Bibliography Management Tool

Related Links

Report an Issue

Search in Library

There is no full-text available at the moment. Airiti would like to request author's authorization. I would like to provide authorization.

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.
連結：

Times Cited (5) 〈TOP〉

Altmetrics

〈TOP〉

E-mail ：

When an article is available to download, a notice will be sent to your mailbox address.

E-mail ：