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1、ChemicalScienceViewArticleOnlineEDGEARTICLEViewJournal
2、ViewIssueHigh-throughputidentificationofGprotein-coupledreceptormodulatorsthroughaffinitymassCitethis:Chem.Sci.,2018,9,3192spectrometryscreening†abcbadShanshanQin,‡MengmengMeng,‡DehuaYang,‡WenwenBai,‡
3、YanLu,aaaaadeYaoPeng,GaojieSong,YiranWu,QingtongZhou,SuwenZhao,XipingHuang,eccefJohnD.McCorvy,XiaoqingCai,AntaoDai,BryanL.Roth,MichaelA.Hanson,adcdgadadZhi-JieLiu,Ming-WeiWang,*RaymondC.StevensandWenqingShui*Gprotein-coupledreceptors(GPCRs)representthe
4、largestclassofcellsurfaceproteinsandthusconstituteanimportantfamilyoftherapeutictargets.Therefore,significantefforthasbeenputtowardstheidentificationofnovelligandsthatcanmodulatetheactivityofaGPCRtargetwithhighefficacyandselectivity.However,duetolimitations
5、inherenttothemostcommontechniquesforGPCRliganddiscovery,thereisapressingneedformoreefficientandeffectiveligandscreeningmethodsespeciallyCreativeCommonsAttribution3.0UnportedLicence.fortheidentificationofpotentialallostericmodulators.Herewepresentahigh-thro
6、ughput,label-freeandunbiasedscreeningapproachfortheidentificationofsmallmoleculeligandstowardsGPCRtargetsbasedonaffinitymassspectrometry.Thisnewapproachfeaturestheusageoftarget-expressingcellReceived31stOctober2017membranesratherthanpurifiedproteinsforliga
7、ndscreeningandallowsthedetectionofbothAccepted19thFebruary2018orthostericandallostericligandstargetingspecificGPCRs.ScreeningasmallcompoundlibrarywiththisDOI:10.1039/c7sc04698gapproachledtotherapiddiscoveryofanantagonistforthe5-HTreceptorandfourpositive
8、allostericrsc.li/chemical-sciencemodulatorsforGLP-1receptorthatwerenotpreviouslyreported.Thisarticleislicensedunderareceptorfunctionalassays,whichmeasureGPCRdownstreamIntroductionsignalingeffectors,3areinadequateforidentifyingallostericorThesuperfamilyo
9、fG-protein-coupledreceptors(GPCRs)isthebiasedsignalingmodulatorsandoengeneratehitsunsuitableforsubsequentoptimization.4Radioligandbindingassays,largestclassofcellsurfacereceptorsandtheyplayacentralroleOpenAccessArticle.Publishedon20Feb