资源描述：
《DNA templatedDNA模板地有机合成.pdf》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。
1、DNA-TemplatedOrganicSynthesisMatthewCoulterOrganic-BiologicalSeminarDepartmentofChemistryUniversityofTorontoFebruary4,2008DNA-TemplatedOrganicSynthesisDavidR.LiuProfessorofChemistryandChemicalBiologyHarvardUniversity•Smallmoleculelibrarysynthesis•DNAassistedreactiondiscovery2DNA-TemplatedSynth
2、esisTranscriptionTranslationDNAProteinDNASyntheticcompound3DNA-TemplatedOrganicSynthesisConventionalScreeningApproachDNA-Templated-Approach•spatialseparationgenerallyrequired•Allmoleculessynthesizedinonepot•eachcompoundanalyzedindividually•Allmoleculesanalyzedsimultaneously•adequatematerialreq
3、uiredforscreen•fmol-nmolscale•workloadincreaseswithsamplesize•workloaddoesnotscalewithsamplesize•Syntheticcompoundlibrarysize109–1013•Modernhigh-throughputscreeningfacility•9–9000years•Tools:MS,NMR,HPLCetc.•Tools:molecularbiology4Rozenman,M.M.;McNaughton,B.R.,Liu,D.R.Curr.Opin.Chem.Biol.2000,1
4、1,259-268.CanDNAEncodeChemicalReactions?Strategy:LinknucleophileandelectrophiletoseparatestrandsofcomplementaryDNAReagentTemplate60nM60nM5Gartner,Z.J.;Liu,D.R.J.AmChemSoc.2001,123,6961-663.ASequenceSpecificSyntheticReactionMismatches:0303ProductTemplatetemplate1min20min•Bondformationoccurssequ
5、encespecifically•Verylowbackground(non-templated)reactivityduetoverylowreagentconcentrations•DNAencodedreaction6Gartner,Z.J.;Liu,D.R.J.AmChemSoc.2001,123,6961-663.MultipleReactionTypesSupportedAllsubstratestestedreactedsequence-specifically:M=matched;X=mismatchedProductTemplate1:1template:reag
6、entpH7.5,25oC,16hMXProductTemplateMX1:1template:reagentpH7.5,25oC,10min7Gartner,Z.J.;Liu,D.R.J.Am.Chem.Soc.2001,123,6961-663.ScopeofDNA-TemplatedReactivityManystandardreactionsareencodedsequencespecificallyatnMconcentrationsofreactants:Reductiveamination:Amidebondformation:Henryreaction:8Gartn
7、er,Z.J.;Kannan,M.W.;Liu,D.R.Angew.Chem.Int.Ed.2002,41,1796-1800.ScopeofDNA-TemplatedReactivityNitro-Michael:WittigReaction:1,3dipolarcycloaddition:HeckReaction:9Gartner,Z.J.;Kannan,M.W.;Liu,D.R.Angew.Chem.Int.Ed.2002,41,1796-1800.ASynth
