TraditionalChinesemedicinetargetidentificationbasedonTargetFishingstrategy

摘要： OBJECTIVEOurgroupmainlyfocusesonthetargetidentificationandpharmacologicalmechanismstudyofTCM.WedeeplyidentifiedthedirecttargetsoftheactiveingredientsinTCMusingmoleculeprobe-TargetFishingtechnologyinchemicalbiology,andexploredtherelatedsignalingpathwaystoexplainthetraditionalefficiencyofTCM.METHODSWesynthesizedbiotin-taggedmole.culeprobebyconnectingbiotintagtoTCMactivemoleculeusingPGEasalinker.Then,thebiotintaggedmoleculeprobewasboundtothesurfaceofsolidbeadsbystrongbiotin-avidininteraction.Thus,themoleculeprobe-boundbeadsweremixedwithcelllysatestocapturethepotentialtargetsandidentifiedbyMS.RESULTSOurstudyfoundthatSAwhichwasananti-inflammatorycompound.couldselectivelybindtoIMPDH2inmicroglialcells,andSAshowedweakeranti-inflammatoryeffectonIMPDH2-knockdownmicroglialcells,suggestingIMPDH2asakeyanti-inflammatorytargetforSA.Ad.ditionally,handelinwasakeyanti-inflammatorycompound.WeidentifiedthetargetproteinofhandelinasHsp70frommicroglialcellsusingtargetpull-downtechnology.Moreover,handelinshowedweakeranti-inflammatoryeffectonHsp70-knockdownmicroglialcells,revealingthatHsp70wasthedirectantiinflammatorytargetofhandelin.CONCLUSIONOurstudyprovidedmethodologyreferencesforTCMtargetidentificationinthefuture,andalsoshowedanewinsightforexploringthepharmacologicalmechanismofTCMactiveingredients.Moreimportantly,wecanperformscientificannotationforTCMefficiencybyclarifyingthebiologicalfunctionsofeachtargetprotein,showingimportantsignificanceonmodernizationandinternationalizationofTCM. ... （共1页）