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1、AdvancedDrugDeliveryReviews65(2013)1357–1369ContentslistsavailableatScienceDirectAdvancedDrugDeliveryReviewsjournalhomepage:www.elsevier.com/locate/addrFusionproteinlinkers:Property,designandfunctionality☆XiaoyingChen,JennicaL.Zaro,Wei-ChiangShen⁎DepartmentofPharmaco
2、logyandPharmaceuticalSciences,SchoolofPharmacy,UniversityofSouthernCalifornia,LosAngeles,CA90089,USAarticleinfoabstractArticlehistory:Asanindispensablecomponentofrecombinantfusionproteins,linkershaveshownincreasingimportanceinReceived3July2012theconstructionofstable,
3、bioactivefusionproteins.Thisreviewcoversthecurrentknowledgeoffusionpro-Accepted20September2012teinlinkersandsummarizesexamplesfortheirdesignandapplication.Thegeneralpropertiesoflinkersde-Availableonline29September2012rivedfromnaturally-occurringmulti-domainproteinsca
4、nbeconsideredasthefoundationinlinkerdesign.Empiricallinkersdesignedbyresearchersaregenerallyclassifiedinto3categoriesaccordingtotheirstruc-Keywords:tures:flexiblelinkers,rigidlinkers,andinvivocleavablelinkers.Besidesthebasicroleinlinkingthefunction-Bifunctionalrecombin
5、antproteinsSpaceraldomainstogether(asinflexibleandrigidlinkers)orreleasingthefreefunctionaldomaininvivo(asininPharmacokineticsvivocleavablelinkers),linkersmayoffermanyotheradvantagesfortheproductionoffusionproteins,suchasPharmacodynamicsimprovingbiologicalactivity,inc
6、reasingexpressionyield,andachievingdesirablepharmacokineticprofiles.©2012ElsevierB.V.Allrightsreserved.Contents1.Introduction.............................................................13572.Generalpropertiesoflinkersderivedfromnaturally-occurringmulti-domainproteins
7、...........................13583.Empiricallinkersinrecombinantfusionproteins............................................13593.1.Flexiblelinkers.........................................................13593.2.Rigidlinkers...............................................
8、...........13613.3.Invivocleavablelinkers.....................................................13613.4.Summaryofempiricallinkers....
