The new Immunosuppressant, isogarcinol, binds directly to itstarget enzyme calcineurin, unlike cyclosporin A and tacrolimus
作者单位：Department of Biochemistry and Molecular Biology Beijing Normal University Gene engineering and Biotechnology Beijing Key Laboratory
会议名称：《中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议》
会议日期：2014年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
关 键 词：isogarcinol calcineurin isothermal titration calorimetry fluorescences pectroscopy docking
摘 要：Isogarcinol, a bioactive polyisoprenylated benzophenone derivative isolated fromGarcinia mangostana L., has been shown previously to exert a strong inhibitory effect oncalcineurin and is thus a potential oral, low-toxicity immunomodulatory drug. In thepresent study, enzyme kinetic analysis showed that inhibition of calcineurin by isogarcinolwas competitive. Fluorescence spectroscopy indicated that isogarcinol bound to *** titration calorimetry showed that binding was mainly driven by enthalpy,and was exothermic because the enthalpy change exceeded the entropy reduction. The interactionforce is either hydrogen bonding or Van der Waals forces. Fluorescence resonanceenergy transfer and molecular docking experiments indicated that there were twopotential binding sites for isogarcinol in the catalytic domain of calcineurin. In summary,isogarcinol binds directly to calcineurin in vitro, unlike the classical calcineurin inhibitorscyclosporin A and tacrolimus.