資源描述：
《Peptide Synthesis Protocols 多肽合成寶典》由會(huì)員上傳分享，免費(fèi)在線閱讀，更多相關(guān)內(nèi)容在行業(yè)資料-天天文庫(kù)。
1、CHAPTER1ProcedurestoImproveDifficultCouplingsMichaeZW.PenningtonandMichaelE.Byrnes1.IntroductionThesuccessfulcouplingofaminoacidderivativesduringthesynthe-sisofapeptidebyeithersolutionorsolid-phaseproceduresdependsonboththereactivityofthecarboxylgroupoft
2、heN-protectedaminoacidandthestericaccessibilityofthereactivenucleophile(eitheraprimaryorsecondaryamine).Activationofthecarboxylgroupisarequisiteforthesynthesisofanamidebond.Manyactivationprocedureshavebeendevelopedtoaccomplishthis,andultimately,thereacti
3、vityoftheacti-vatedspeciesiscrucialindeterminingthecouplingyield.Improvementsinsolid-phaseassemblytechniquesnowpermittherou-tinesynthesisoflong(>40residues)complexpeptides.However,astheabilitytoassembletheselongermoleculesonasolid-phasematriximproved,new
4、problemswereencountered.Successfulsynthesiswashamperedbystericfactorsofthebulkyprotectedderivatives(I),inter-molecularaggregationoftheprotectedpeptidechain(2,3),formationofhydrogenbondingstructures,suchasP-sheet(4-7),prematuretermina-tion,orcyclizationon
5、theresin(a-10).Ourlaboratoryroutinelysynthesizeslargequantitiesofmanypeptides.Weemployasemiautomatedprocedurewhereeachindividualcouplingismonitoredforcompletenesspriortothenextdeblocking/elongationstep.Asaresultofthistypeofstrategy,weencountermanycouplin
6、gsFrom:MethodsmMolecularB!olagy,Vol.35:PeptldeSynthewsProtocolsEditedby:M.W.PennmgtonandBM.DunnCopyright01994HumanaPressInc.,Totowa,NJ12PenningtonandByrnesthatdonotproceedtocompletenessusingeitherasinglecarbodiimide/HOBTcoupling(II)ordoublecouplingemploy
7、ingthesamecarbo-diimide/HOBTstrategy.Duringthepastseveralyears,wehaveevalu-atedmanyofthemethodsdescribedintheliteraturetoimprovethecouplingyield.Itisimportanttopointoutthateverypeptidepresentsitsownuniquesetofcomplications.Thus,itisimpossibletogiveaunive
8、r-salprocedurethatwillworkforeverypeptide.Itisthepurposeofthischaptertopresentseveraloftheseprotocols,whichwehavefoundtobeveryuseful.2.Materials1.Allmaterialsandreagentsarepurchasedfromcommercialsourcesandusedassuch.2.Synt
