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《Impact of Hydrophobic Chain Composition on AmphiphilicMacromolecule Antiatherogenic Bioactivity疏水链组成对两亲性的影响 高分子抗动脉粥样硬化生物活性》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、ThisisanopenaccessarticlepublishedunderanACSAuthorChoiceLicense,whichpermitscopyingandredistributionofthearticleoranyadaptationsfornon-commercialpurposes.Articlepubs.acs.org/BiomacImpactofHydrophobicChainCompositiononAmphiphilicMacromoleculeAntiatherogenicBioactivity†‡‡,§,†
2、,‡AllisonFaig,LatrishaK.Petersen,PrabhasV.Moghe,andKathrynE.Uhrich*†‡§DepartmentofChemistryandChemicalBiology,DepartmentofBiomedicalEngineering,andDepartmentofChemicalandBiochemicalEngineering,RutgersUniversity,Piscataway,NewJersey08854,UnitedStates*SSupportingInformationAB
3、STRACT:Amphiphilicmacromolecules(AMs)composedofsugarbackbonesmodifiedwithbranchedaliphaticchainsandapoly(ethyleneglycol)(PEG)tailcaninhibitmacrophageuptakeofoxidizedlow-densitylipoproteins(oxLDL),amajoreventunderlyingatherosclerosisdevelopment.PreviousstudiesindicatethatAMhy
4、drophobicdomainsinfluencethisbioactivitythroughinteractingwithmacrophagescavengerreceptors,whichcancontainbasicand/orhydrophobicresidueswithintheirbindingpockets.Inthisstudy,wecomparetwoclassesofAMstoinvestigatetheirabilitytopromoteathero-protectivepotencyviahydrogen-bonding
5、orhydrophobicinteractionswithscavengerreceptors.Aseriesofether-AMs,containingmethoxy-terminatedaliphaticarmscapableofhydrogen-bonding,wassynthesized.ComparedtoanalogousAMscontainingnoethermoieties(alkyl-AMs),ether-AMsshowedimprovedcytotoxicityprofiles.IncreasingAMhydrophobic
6、ityviaincorporationoflongerand/oralkyl-terminatedhydrophobicchainsyieldedmacromoleculeswithenhancedoxLDLuptakeinhibition.ThesefindingsindicatethathydrophobicinteractionsandthelengthofAMaliphaticarmsmoresignificantlyinfluenceAMbioactivitythanhydrogen-bonding.1.INTRODUCTIONcondi
7、tions),andasaresultoftheirsystemicadministrationandmechanismofactionstatinsdonotdirectlytreatatherogenicAtherosclerosis,amajorcauseofmortalityworldwide,isan10−12inflammatorydiseasecharacterizedbyarterialplaquedevelop-sitesinthearteries.Whenstatinsarenottoleratedbyment.1−5Dur
8、ingtheearlystagesofatherosclerosis,low-densitypatientsorwhenpatientsaregenetically