抗菌肽作用机制及应用研究进展_刘世财

Δ[e-mail][e-mail]。。。。Ｒ978.1ADOI10.3969/j.issn.1005-1678.2016.04.05AdvanceinmechanismandapplicationofantibacterialpeptideLIUShi-caiFANLin-linZHENGHengΔZHANGQiu-yiSchoolofLifeScienceandTechnologyChinaPharmaceuticalUniversityNanjing210009ChinaAbstractIntheeraofoutbreakingofantibioticresistancethediscoveryofnewantibacterialdrugsisemergent.Antimicrobialpeptidesareimportantcomponentsofthenaturaldefensesofmostlivingorganismsagainstinvadingpathogens.Theuniqueantibacterialmechanismdirectbactericidaleffectrelativelyslowofresistanceacquirementandcanusedaloneorcombinedwithantibioticsmakeantimicrobialpeptidesbeattractivepotentialantibacterialdrugs.Inthispaperwereviewthephysicochemicalpropertyofantibacterialpeptidesactionmechanismanddesignofantimicrobialpeptidesandgiveabriefintroductionofseveralpromisingantimicrobialpeptides．Keywordsantibioticresistanceantimicrobialpeptidesactionmechanismdesignofantimicrobialpeptidesapplicationprogress1928Fleming1。。2-4。。antimicrobialpeptidesAMPs。、5。6。。。、、5。。。112～60。、30%。+2～+9。NMＲ5①α②HNP-1HNP-2HNP-3③β④、⑤。。。—02—20164367。。1.1barrel-stavemodel。。。1.2carpetmodeldermaseptin8。“”。。①②③9。1.3toroidalporemodel。Yoneyama10YoneyamalacticinQ。LacticinQ4.6nm。1.4aggregatemodel。—。。1.5DNA、ＲNA、11。Shai12。pp-39apidaecin。。bac-5bac-7pp-39bac-5bac-7。-1-1DNA13。LF11-322PFＲPFWＲIＲIＲＲ-NH2Lu14PFＲDNA。215。。。16。。2①C、1、、、。②α－α－、、、。IsCTLee17IsCTILGKIWEGIKSLF-NH25IsCTK7P8K11-IsCTIsCT。TryptophanfluorescenceK7P8K11-IsCT。Lv1836PMAP-36C12N24GI24GＲFＲＲLＲKKTＲKＲLKKIGKVLKWI-NH2GI24PMAP-3624PMAP-36。GI24。GI2423。GI24。SEMTEMGI24。Panteleev19-20β-hairpinarenicin-1ＲWCVYAYVＲVＲGVLVＲYＲＲCW、617arenicin-1ALP。ALP1ＲWCVYAＲVＲGVＲYＲＲCW50μM。ALP1arenicin-1。。ALParenicin-1membrane-mimicking。β-hairpin。3FDA101。—12—2016436。。250011、。、MU1140。2。12010-2014FDATab.1Approvedpeptide-baseddrugsbytheFDA2010-2014LiraglutideVictozaⅡ201021TelaprevirBoceprevirIncivekVictrelis201120112121ThrombogenicsOcriplasminJetrea201221CarfilzomibKyprolis201221PasireotideSignifor201221AfymaxPeginesatideOmontys201221DiscoveryLabsLucinactantSurfaxin201221LixisenatideLyxumiaⅡ201321AlbiglutideTanzeumⅡ201421-222Tab.2Anti-microbialpeptidesindevelopmentorinclinicaltrialsGenaeraPexigananIII23BioWestTherapeuticsOmigananindolicidinIII24-25OctoPlusOP-145LL-37II26NovaBioticsNovexatinII26LytixBiopharmaLytixarLTX-109II26NovactaNVB302BI26OragenicMU114026NovozymePlectasinNZ211427pexigananGIGKFLKKAKKFGKA-FVKILKK。。GenaeraIII—22—2016436。23。Kulkarni28。omigananindolicidinILＲWPWWPWＲＲK-NH2。24。BioWestTherapeuticsOmigananIII。Ｒaventos29PlectasinNZ2114。PlectasinNZ2114pseudoplectanianigrellaLipidⅡ。MIC0.125～0.5mg/LMIC32～≥128mg/L。PlectasinG、30。NZ211427。MU1140Streptococcusmutans22LipidⅡ31。Ghobrial32MU1140MU1140VＲEF。OragenicsIntrexon2012MU1140。OragenicsFDAMU1140MU114026。4、、、。。、、、、。。。、。1BentleyＲ．ThedevelopmentofpenicillingenesisofafamousantibioticJ．PerspectBiolMed2005483444-452．2SilverLL.ChallengesofantibacterialdiscoveryJ．ClinMicrobiolＲev201124171-109．3TaubesG.ThebacteriafightbackJ．Science20083215887356-361．4TorresC.UpagainstthewallJ．NatMed2010166628-631．5MangoniM.BhuniaA.EditorialAntimicrobialPeptidesinMedicinalChemistryAdvancesandApplicationsJ．CurrTopMedChem20161612-3．6ZhuXDongNWangZetal.Designofimperfectlyamphipathicα-helicalantimicrobialpeptideswithenhancedcellselectivityJ．ActaBiomater2014101244-257．7ChoiHＲangarajanNWeisshaarJC.LightsCameraActionAntimicrobialPeptideMechanismsImagedinSpaceandTimeJ．TrendsMicrobiol2016242111-122．8DaganAEfronLGaidukovLetal.InvitroantiplasmodiumeffectsofdermaseptinS4derivativesJ．AntimicrobAgentsChemother20024641059-1066．9MatsuzakiKSugishitaKIshibeNetal.Ｒelationshipofmembranecurvaturetotheformationofporesbymagainin2J．Biochemistry1998373411856-11863．10YoneyamaFImuraYOhnoKetal.Peptide-lipidhugetoroidalporeanewantimicrobialmechanismmediatedbyalactococcalbacteriocinlacticinQJ．AntimicrobAgentsChemother20095383211-3217．11ZhangLJGalloＲL.AntimicrobialpeptidesJ．CurrBiol2016261Ｒ14-19．12ShaiY．Mechanismofthebindinginsertionanddestabilizationofphospholipidbilayermembranesbyalpha-helicalantimicrobialandcellnon-selectivemembrane-lyticpeptidesJ．BiochimBiophysActa199914621-255-70．13TossiASandriLGiangasperoA.Amphipathicalpha-helicalantimicrobialpeptidesJ．Biopolymers20005514-30．14LuYZhangTFShiYetal.PFＲpeptideoneoftheantimicrobialpeptidesidentifiedfromthederivativesoflactoferrininducesnecrosisinleukemiacellsJ．SciＲep2016620823．15TyagiAKapoorPKumarＲetal.InSilicoModelsforDesigningandDiscoveringNovelAnticancerPeptidesJ．SciＲep201332984．16PowersJPHancockＲE.TherelationshipbetweenpeptidestructureandantibacterialactivityJ．Peptides200324111681-1691．17LeeKShinSYKimKetal.Antibioticactivityandstructuralanalysisofthescorpion-derivedantimicrobialpeptideIsCTanditsanalogsJ．BiochemBiophysＲesCommun20043232712-719．18LvYWangJGaoHetal.Antimicrobialpropertiesandmembrane-activemechanismofapotentialα-helicalantimicrobialderivedfromcathelicidinPMAP-36J．PLoSOne201491e86364．19PanteleevPVBolosovIABalandinSVetal.DesignofantimicrobialpeptidearenicinanalogswithimprovedtherapeuticindicesJ