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1、JournalofInorganicBiochemistry117(2012)298–305ContentslistsavailableatSciVerseScienceDirectJournalofInorganicBiochemistryjournalhomepage:www.elsevier.com/locate/jinorgbioGold-phosphinebindingtodenovodesignedcoiledcoilpeptidesa,⁎,GemmaA.BullenabbAnnaF.A.Peacock,LeeA.Gethings,
2、JonathanP.Williams,ccFrederikH.Kriel,JudyCoatesaSchoolofChemistry,UniversityofBirmingham,Edgbaston,BirminghamB152TT,UKbWatersCorporation,AtlasPark,Simonsway,Wythenshawe,ManchesterM225PP,UKcBiomed,AdvancedMaterialsDivision,Mintek,PrivateBagX3015,Randburg2125,SouthAfricaarticl
3、einfoabstractArticlehistory:Thecoordinationofthetherapeuticallyinteresting[AuCl(PEt3)]tothedenovodesignedpeptide,TRIL23C,Received13March2012underaqueousconditions,isreportedhere.TRIL23CrepresentsanidealmodeltoinvestigatethebindingReceivedinrevisedform3May2012of[AuCl(PEt)]tos
4、mallproteinsinanefforttodevelopnovelgold(I)phosphinepeptideadductscapable3Accepted21May2012ofmimickingbiologicalrecognitionandtargeting.ThisisduetothesmallsizeofTRIL23C(30aminoAvailableonline2June2012acids),yetstablesecondaryandtertiaryfold,symmetricnatureandtheavailabilityo
5、fonlyonethiolbindingsite.[AuCl(PEt3)]wasfoundtoreactreadilywiththeCyssidechainina1:1ratioasconfirmedbyUV-visible,Keywords:31DenovopeptidePNMRandmassspectrometry.Circulardichroismconfirmedthatthecoiledcoilstructurewasretainedon+Coiledcoilcoordinationofthe{Au(PEt3)}unit.Redesign
6、oftheexteriorofTRIL23Cbasedonabiologicallyrelevantrec-ProteindesignognitionsequencefoundinGCN4,didnotalterthecoordinationchemistryof[AuCl(PEt3)].TothebestofourGoldphosphineknowledge,thisrepresentsthefirstreportonthecoordinationofgold(I)phosphinecompoundstodenovoAuranofindesign
7、edpeptides,andcouldleadtothegenerationofnovelgold(I)phosphinepeptidetherapeuticsinthefuture.©2012ElsevierInc.Allrightsreserved.1.Introductioncellpenetratingpeptides(CPPs)andtumourtargetingsequencessuchasRGD.Thesearchfornewandimprovedmetalbaseddrugsisfueledpri-Reportsexistint
8、heliteratureofshortpeptidegold(I)phosphinemarilybythesuccessofthefirstplatin