Spectroscopic studies of the interaction between phosphorus heterocycles and cytochrome P450  

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作  者:Dumei Ma Libo Zhang Yingwu Yin Yuxing Gao Qian Wang 

机构地区:[1]Department of Chemical and Biochemical Engineering,College of Chemistry and Chemical Engineering,Xiamen University,Xiamen,361005,Fujian,China [2]Department of Chemistry and Biochemistry,University of South Carolina,Columbia,SC,29208,USA [3]Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province,College of Chemistry and Chemical Engineering,Xiamen University,Xiamen,361005,Fujian,China

出  处:《Journal of Pharmaceutical Analysis》2021年第6期757-763,共7页药物分析学报(英文版)

基  金:supported by the China Scholarship Council and Fujian University-Industry Research Cooperation Project(Project No.:2018N5013)。

摘  要:P450 fatty acid decarboxylase Ole T from Staphylococcus aureus(Ole TSA)is a novel cytochrome P450 enzyme that catalyzes the oxidative decarboxylation of fatty acids to yield primarily terminal alkenes and CO_(2) or minor a-andβ-hydroxylated fatty acids as side-products.In this work,the interactions between a series of cycloalkyl phosphorus heterocycles(CPHs)and Ole TSAwere investigated in detail by fluorescence titration experiment,ultraviolet-visible(UV-vis)and31 P NMR spectroscopies.Fluorescence titration experiment results clearly showed that a dynamic quenching occurred when CPH-6,a representative CPHs,interacted with Ole TSAwith a binding constant value of 15.2×104 M-1 at 293 K.The thermodynamic parameters(ΔH,ΔS andΔG)showed that the hydrogen bond and van der Waals force played major roles in the interaction between Ole TSAand CPHs.The UV-vis and31 P NMR studies indicated the penetration of CPH-6 into the interior environment of Ole TSA,which greatly affects the enzymatic activity of Ole TSA.Therefore,our study revealed an effective way to use phosphorus heterocyclic compounds to modulate the activity of cytochrome P450 enzymes.

关 键 词:Phosphorus heterocycles Cytochrome P450 Ole T INTERACTION SPECTROSCOPY 

分 类 号:R965[医药卫生—药理学]

 

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