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1、Ne神经化学DOI----NeurochemistryDOI.uroDOI:10.1002/anie.201209885DevelopmentofaPlatinumComplexasananti-AmyloidAgentfortheTherapyofAlzheimer_sDisease铂复杂的发展作为一个种抗体代理Alzheimer_s疾病的治疗VijayaB.Kenche,LinW.Hung,KeylaPerez,IreneVolitakes,GuiseppeCiccotosto,JeffreyKwok,NicoleCritch,NikkiSher
2、ratt,MikhalinaCortes,VarshaLal,ColinL.Masters,KazumaMurakami,RobertoCappai,PaulA.Adlard,andKevinJ.Barnham*林Vijayab.Kenchew.挂Keyla佩雷斯,IreneVolitakesGuiseppeCiccotosto,妮可不久后,尼基中,杰弗里·郭Mikhalina议会,VarshaLal,科林·l·大师Kazuma村上,RobertoCappaiPaula.埃德拉德合作,凯文·j·Barnham*Alzheimer_sdisease(A
3、D)isanage-relatedneurodegenerativedisease.Itspathologicalindicatorsincludeextracellularamyloidplaques,themainconstituentofwhichistheamyloidb-peptide(Ab),andneurofibrillarytanglescomposedofhyperphosphorylatedtauprotein.[1]CurrentevidencesuggeststhattheaggregationofAbsdrivesthedi
4、seaseprocess,asvariousformsofaggregatedAbhavebeenshowntobetoxic,[2]resultinginthedevelopmentofavarietyoftherapeuticstrategiesthattargetAb.[3–6]Todate,mostAbaggregationinhibitorshavebeendesignedtotargetthehydrophobiccentralandC-terminalregionsofAb,whichareingeneralconjugatedpoly
5、aromaticmoleculesthatareveryhydrophobic.[7]Herein,wereportadifferentapproachtothedesignofaggregationinhibitorsofAbanddemonstratethatthisapproachcanmodifyAbinvivo.Abcontainsametalbindingmotifwiththreehistidineresidues(6,13,and14)neartheNterminus,andtheinteractionofthissitewithzi
6、ncandcoppermodulatestheaggregationandtoxicityofAb.[8,9]Wehavepreviouslytakenadvantageofthemetal-bindingabilityofAbtoshowthatcommerciallyavailablePtIIcomplexesof1,10-phenanthrolineligandstargetthissite,thusinhibitingAbaggregationinvitro.[10]Foravarietyofreasons,includinglackofno
7、velty,cumbersomemulti-stepsyntheticprocedures,[11,12]andpoorbioavailability,thesecomplexesareunsuitableforinvivostudies.ThereforewesoughttoidentifynewPtcomplexesthataresuitableforinvivostudies.Alzheimer_s病(AD)是一种与年龄相关的神经退行性疾病。其病理指标包括细胞外淀粉样斑块,主要成分是淀粉样b-peptide(Ab),和神经原纤维缠结由hyper
8、phosphorylatedtau蛋白质。[1]目前证据表明,Abs驱动疾病的聚合过程中,由于各种形式的聚合
