基于Scatchard法的碳酸酐酶-脂质体与药物结合常数测定.pdfVIP

科技导报2015，33（17） 基于基于ScatchardScatchard法的碳酸酐酶法的碳酸酐酶--脂质体脂质体 与药物结合常数测定与药物结合常数测定 胡英慧，戴荣继，安静，钱庆庆，邓玉林 北京理工大学生命学院，北京 100081 摘要摘要 为更好地模拟药物小分子与碳酸酐酶在体内的相互作用，采用碳酸酐酶-脂质体毛细管电泳法，以4-羧基苯磺酰胺为分 析对象建立碳酸酐酶药物筛选模型，并以此模型为基础计算12种药物小分子与碳酸酐酶的结合常数，分析药物小分子与碳酸酐 4 -1 酶的相互作用。结果表明，4-羧基苯磺酰胺与碳酸酐酶-脂质体的结合常数为1.172×10 mL·g ，具有较强的相互作用。基于 此，筛选出4种（咖啡酸、L-抗坏血酸、2,4-二氯-5-磺酰胺基苯甲酸和4-氯-3-磺酰胺基苯甲酸）和5种（阿魏酸、马兜铃酸、没 食子酸、原儿茶酸、烟酸）与复合物具有较强或较弱相互作用的药物。通过该法可快速、有效、经济地测定碳酸酐酶或其他靶标与 药物的相互作用，缩短药物研发周期。 关键词关键词 脂质体；碳酸酐酶；毛细管电泳 中图分类号中图分类号 O652 文献标志码文献标志码 A doidoi 10.3981/j.issn.1000-7857.2015.17.011 Bindinginteractionofcarbonicanhydrase-liposomecomplexand medicinalmoleculesbyScatchardmethod HUYinghui,DAIRongji,ANJing,QIANQingqing,DENGYulin SchoolofLifeScience,BeijingInstituteofTechnology,Beijing 100081,China AbstractAbstract Inthis invitro study,carbonicanhydrase-liposomecomplexwaspreparedtosimulatethe invivo interactionsbetweendrug moleculesandcarbonicanhydrase.Thecomplexwaspreparedbyultrasoniccelldisruption,mixingandextrusion.Zetapotentialand thesizeofcarbonicanhydrase-liposomecomplexwere-45.06 mVand 99.43 nm,respectively,indicatingthiscomplexisstableand suitable to apply for capillary electrophoresis. The complex was further added in running buffers as pseudo stationary phase in -3 capillaryelectrophoresis,and 4-carboxybenzenesulfonamide(containing 2.2×10 mol/L 4-methyl-2-pentanoneasEOFmarker)was added as a sample to establish the model of the interaction between the drug and carbonic anhydrase-liposome complex using 4 -1 Scatchardmethod.Thebindingconstantinthismodelwas 1.172×10 mL·g .Amongthe 12drugsstudiedusingthismethod,caffeic acid,L-ascorbicacid,