点击化学和生物正交反应.ppt

,点击化学和生物正交反应在生物分子标记中的前所未有的选择性,导师:熊博报告人:吴蔚学号：2010111924,Outline文献背景“点击化学”、正交实验的定义及特征在药物开发中的应用生物正交反应标记生物分子成像展望,文献背景,“点击化学”正交设计实验,点击化学的提出者,BarrySharpless,点击化学:选用易得原料，通过可靠，高效而又具选择性的化学反应来实现碳杂原子连接(C-X-C)，低成本快速合成大量新化合物的一套强大的，实用的合成方法,点击化学定义,连接方式(C-X-C)：Generatesubstancesbyjoiningsmallunitstogetherwithheteroatomlinks；热力学驱动力：highthermodynamicdrivingforce(20kcal/mol)过程标准:Modular,wideinscope,giveveryhighyields,generateonlyinoffensivebyproductsthatcanberemovedbynonchromatographicmethods,stereo-specific,simplereactionconditions,readilyavailablestartingmaterialsandreagents,useofnosolventorasolventthatisbenignoreasilyremoved,andsimpleproductisolation;,定义及特征,点击化学是指选用易得原料，通过可靠，高效而又具选择性的化学反应来实现碳杂原子连接(C-X-C)，低成本快速合成大量新化合物的一套强大的，实用的合成方法。,点击化学的特征,连接方式(C-X-C)：Generatesubstancesbyjoiningsmallunitstogetherwithheteroatomlinks热力学驱动力：highthermodynamicdrivingforce(20kcal/mol),过程标准:Modular,wideinscope,giveveryhighyields,generateonlyinoffensivebyproductsthatcanberemovedbynonhromatographicmethods,stereo-specific,simplereactionconditions,readilyavailablestartingmaterialsandreagents,useofnosolventorasolventthatisbenignoreasilyremoved,andsimpleproductisolation,点击化学反应特征,点击化学的优点,highyieldseasytoperform,widescopefastersynthesis,productisolationmustbesimpleinsensitivetooxygenorwater,readilyavailablereagentshighlyselectivereactions,thermodynamicdrivingforce20kcal/mol,正交试验设计：研究多因素多水平的又一种设计方法，它是根据正交性从全面试验中挑选出部分有代表性的点进行试验特点：“均匀分散，齐整可比”，高效率、快速、经济,用正交法设计测试用例正交表的构成,点击化学反应类型1.STRATEGYOFCLICKCHEMISTRYANDBIOORTHOGONALREACTIVITY1.1.叠氮，炔烃环加成反应Azide-AlkyneCycloaddition.1.2.自由铜叠氮，炔烃环加成反应Copper-FreeAzide-AlkyneCycloaddition.1.3.道丁格连接反应StaudingerLigation.1.4.其他反应OtherReactions.1.5.比较生物正交反应条件ComparisonofBioorthogonalReactionsandConditions.,2.IMPACTSOFCLICKCHEMISTRYONDRUGDEVELOPMENT,DerivatizationofLipidProbes.Modification.LabelingofNucleotidesforImagingDNAandRNA.,IntroductionofUnnaturalAminoAcidsBearingReactiveTagsintoProteins.LabelingofViralSurfaces.,IncorporationofLabeledProbesontoProteinsviaPostTranslationalActivity-BasedProteinProfiling,3.1,3.2,3.3,3.LABELINGANDIMAGINGOFBIOMOLECULESUSINGBIOORTHOGONALREACTIONS,FIGURE2:Insitucombinatorialdrugdevelopment.(A)Generalschematicfortemplatedinhibitordevelopment.Bindingofreactantsbythetargetenzymeleadstocatalyticformationoftheoptimalinhibitor.(B)Applicationofthisapproachtothedevelopmentofapotentbisubstrateinhibitorofacetylcholinesterase.,FIGURE4:Incorporationofunnaturalaminoacidsintoproteins.(A)Noncanonicalaminoacidsthathavebeenintroducedintoproteins.(B)SchematicforunnaturalaminoacidmutagenesisusingageneticallyengineeredtRNAsynthetase.,FIGURE5:Metaboliclabelingofcell-surfaceglycansusingbioorthogonalchemistry.(A)Azideandalkyne-derivatizedsugarsthatsuccessfullyinfiltratebiosyntheticpathways.(B)Schematicfortheincorporationofsimplesugarderivativesontoglycoproteinsviametabolicpathways,followedbyselectivelabelingthroughbioorthogonalchemistry.,展望,链接化学是一种简单的合成方式，其目的是加速新功能物质和材料的发现，目前尚处于初步发展阶段，但自提出以来，由于其具有反应易得