Exploration of the One-Bead One-Compound Methodology for the Design of Prolyl Oligopeptidase Substrates 英文参考文献.docVIP

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Exploration of the One-Bead One-Compound Methodology for the Design of Prolyl Oligopeptidase Substrates 英文参考文献.doc

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Exploration of the One-Bead One-Compound Methodology for the Design of Prolyl Oligopeptidase Substrates 英文参考文献

ExplorationoftheOne-BeadOne-Compound MethodologyfortheDesignofProlylOligopeptidase Substrates GemmaComellas1,2,ZusannaKaczmarska1,TeresaTarrago′1,MeritxellTeixido′1,ErnestGiralt1,2* 1InstitutdeRecercaBiome`dica (IRBBarcelona),ParcCient?′ficdeBarcelona,Barcelona,Spain,2DepartmentofOrganicChemistry,UniversitatdeBarcelona,Barcelona, Spain Abstract Herewedescribethedesign,synthesisandevaluationofthefirstsolid-phasesubstratesforprolyloligopeptidase(POP),a cytosolicserinepeptidaseassociatedwithschizophrenia,bipolaraffectivedisorderandrelatedneuropsychiatricdisorders. Thisstudyseekstocontributetothefuturedesignofaone-beadone-compound(OBOC)peptidelibraryofPOPsubstrates, basedonanintramolecularenergytransfersubstrate.Unexpectedly,theenzymaticevaluationofthesubstratesattachedon solid-phasebymeansoftheHMBAlinkerwerecleavedthroughtheesterbond,therebysuggestinganunknownesterase activityofPOP,inadditiontoitsknownpeptidaseactivity.Byperformingmultipleactivityassays,wehaveconfirmedthe esteraseactivityofthisenzymeanditscapacitytoprocessthesubstratesonsolid-phase.Finally,wetestedanewlinker, compatiblewithboththesolid-phasepeptide-synthesisusedandtheenzymaticassay,forapplicationinthefuturedesign ofanOBOClibrary. Citation:ComellasG,KaczmarskaZ,Tarrago′ T,Teixido′ M,GiraltE(2009)ExplorationoftheOne-BeadOne-CompoundMethodologyfortheDesignofProlyl OligopeptidaseSubstrates.PLoSONE4(7):e6222.doi:10.1371/journal.pone.0006222 Editor:MaximAntopolsky,UniversityofHelsinki,Finland ReceivedFebruary6,2009;AcceptedJune18,2009;PublishedJuly13,2009 Copyright: ? 2009 Comellas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyMCI-FEDER(Bio2008-00799)andtheGeneralitatdeCatalunya(XRBandGrupsConsolidats).FellowshipsupporttoG.C.was providedbyAgustiPedroiPonsFoundation.Thefundershadnoroleinstudyde