Thecellpenetratingabilityoftheproapoptoticpeptide,KLAKLAKKLAKLAKfusedtotheN-terminalproteintransductiondomainoftranslationallycontrolledtumorprotein,MIIYRDLISHHyoYoungKima,SeunghooKimb,c,HyewonYounb,d,June-KeyChungb,c,d,DongHaeShina,KyunglimLeea,*aCollegeofPharmacy,CenterforCellSignalingandDrugDiscoveryResearch,EwhaWomansUniversity,Seoul,RepublicofKoreabDepartmentofNuclearMedicine,CollegeofMedicine,SeoulNationalUniversity,Seoul,RepublicofKoreacLaboratoryofMolecularImagingandTherapy,CancerResearchInstitute,SeoulNationalUniversity,Seoul,RepublicofKoreadInstituteofRadiationMedicine,MedicalResearchCenter,SeoulNationalUniversity,Seoul,RepublicofKoreaarticleinfoArticlehistory:Received16March2011Accepted29March2011Availableonline12May2011Keywords:ApoptosisCancerMolecularimagingProteintransductiondomainTCTPabstractWeshowhere,thattheproapoptoticpeptide,KLAKLAKKLAKLAK(KLA),whichbyitselfdoesnotpene-tratecellmembranes,candosowhenfusedtoaproteintransductiondomainderivedfromNH2-terminusoftranslationallycontrolledtumorprotein(TCTP-PTD,MIIYRDLISH).Onceinsidethecell,theconjugatedKLAexertsitsproapoptoticactivitytoinhibittumorgrowth.WeevaluatedthecellularuptakeofKLAfusedtoTCTP-PTD(hereaftercalledTCTP-KLA)anditseffectoncancercellviability.TheIC50ofTCTP-KLAwasbetween7and10mmol/L.Wealsoevaluateditsanti-tumoractivityinvivobyinjectingitintoxenograftsoflungcarcinomainBalb/cnudemice.TumorgrowthinhibitionresultingfromtreatmentwithTCTP-KLAwasbetterthanthatofTAT-KLA.TheseresultssuggestthatTCTP-KLAcanbeappliedtodesigncancertherapeutics.�2011ElsevierLtd.Allrightsreserved.1.IntroductionProteintransductiondomains(PTDs),alsonamedcellpene-tratingpeptides(CPPs),aresmallpeptidesconsistingof10e16aminoacidsthatcantraversebiologicalmembrane[1].ThemostwidelystudiedPTDisTAT48-60,derivedfromhumanimmnode-ficiencyvirus(HIV)Tatprotein[2].ItisacationicPTDthatbindselectrostaticallytotheexposedchargedpartsofphospholipids[3].Previously,wereportedthata10-aminoacidpeptide,MIIYRDLISH,derivedfromtheNH2-terminusofhu...
