高中化學(xué)競賽【核酸】課件

核酸NucleicAcids生物分子

(III)1核酸生物分子(III)1§16.1

核酸的基本組成§16.2

核苷Nucleosides§16.3

核苷酸Nucleotides§16.3

核酸NucleoicAcids2§16.1核酸的基本組成§16.2核苷Nucleos核酸(nucleicacids,NA)是存在于細胞核中的生物大分子，載有遺傳信息、指導(dǎo)蛋白質(zhì)合成。因此，核酸是生命的遺傳物質(zhì)，決定生物、生命的個體特征?！?6核酸生物大分子

(III)3核酸(nucleicacids,NA)是存在于細胞核§§16.1

核酸的基本組成核酸的發(fā)現(xiàn)與研究歷史4§16.1核酸的基本組成核酸的4糖(D-核糖、D-2-脫氧核糖)堿基(嘧啶、嘌呤環(huán))磷酸組成核酸的基本成分5糖(D-核糖、D-2-脫氧核糖)組成核酸的基本成分5D-核糖D-2-脫氧核糖糖D-RiboseD-2-Deoxybibose

6D-核糖D-2-脫氧核糖糖D-RiboseD-2-Deoxyβ-D-RibofuranosefoundinDNAβ-D-DeoxyribofuranosefoundinDNA7β-D-Ribofuranoseβ-D-Deoxyribo堿基Cytosine胞嘧啶CThymine胸腺嘧啶TUracil尿嘧啶UPyrimidines(DNA,RNA)(RNA)(DNA)8堿基CytosineThymineUracilPyrimiAdenine腺嘌呤AGuanine鳥嘌呤GPurines(DNA,RNA)(DNA,RNA)9AdenineGuaninePurines(DNA,RN核酸的發(fā)現(xiàn)JohannFriedrichMiescher

(Ger.)1871J.F.MiescherdiscoveredandisolatedNUCLEIN(DNA)inthecellsfrompusinopenwounds.Itbecameknownasnucleicacidafter1874,whenMiescherseparateditintoaproteinandanacidmolecule.FreidrichMiescherfirstdiscoveredDNAin1869.Itwasoriginallycallednuclien.10核酸的發(fā)現(xiàn)JohannFriedrichMiescherItwaswhileworkingonpuscellsatTübingenin1869thatMieschermadehisfundamentaldiscovery.Itwasthoughtthatsuchcellsweremadelargelyofprotein,butMieschernotedthepresenceofsomethingthat"cannotbelongamonganyoftheproteinsubstancesknownhitherto."Infacthewasabletoshowthatitwasnotproteinatall,beingunaffectedbytheprotein-digestingenzymepepsin.Healsoshowedthatthenewsubstancewasderivedfromthenucleusofthecellaloneandconsequentlynamedit'nuclein'.Miescherwassoonabletoshowthatnucleincouldbeobtainedfrommanyothercellsandwasunusualincontainingphosphorusinadditiontotheusualingredientsoforganicmolecules-carbon,oxygen,nitrogen,andhydrogen.Itwasnotuntil1871thatMiescher'spaper,delayedbyHoppe-Seyler(whowantedtoconfirmtheresults),waspublished.Initheannouncedthepresenceofanonproteinphosphorus-containingmoleculeinthenucleiofalargenumberofcells.Justwhatpreciserolethemoleculeplayedinthecellwasnotrevealeduntilthestructureofnucleicacid,asitwasrenamedbyRichardAltmannin1889,wasannouncedbyJamesWatsonandFrancisCrickin1953.MieschercontinuedtoworkonthenucleinextractedfromthespermoftheRhinesalmonfortherestofhisshortlife.Hespentmuchtimepuzzlingonthechemistryoffertilization,evenspeculatingin1874that"ifonewantstoassumethatasinglesubstance...isthespecificcauseoffertilizationthenoneshouldundoubtedlyfirstofallthinkofnuclein."UnfortunatelyMiescherfailedtofollowuphissuggestion,preferringtoexplorephysicalmodelsoffertilization.However,hisworkonnucleinwaseagerlytakenupbyotherorganicchemists,andby1893AlbrechtKosselhadsucceededinrecognizingfournucleicacidbases.

ADictionaryofScientists,OxfordUniversityPress.

FriedrichMiescher(1844-1895)FriedrichMiescherworkedatthePhysiologicalLaboratoryoftheUniversityofBaselandinTübingenandisbestknownforhisdiscoveryofthenucleicacids.11Itwaswhileworkingonpusce1869年，瑞士生化學(xué)家Johann

Friedrich

Miescher由人體的膿組織細胞中分離出一種含多量磷的物質(zhì)并命名為NUCLEIN‘核質(zhì)’。然而核酸這個名詞是在1889年由另一位科學(xué)家Richard

Altmann提出的。In1889,RichardAltmann,F.

Miescher’spupil,introducedtheterm“nucleicacid”.121869年，瑞士生化學(xué)家Johann

Friedrich

核酸的化學(xué)成分–堿基However,Miescher’sworkonnucleinwaseagerlytakenupbyotherorganicchemists,andby1893AlbrechtKosselhadsucceededinrecognizingfournucleicacidbases.AlbrechtKarlLudwigMartinLeonardKossel13核酸的化學(xué)成分–堿基However,Miescher’AlbrechtKosseldiscoveredthatDNAcontainsthebases,adenine(A),cytosine(C),guanine(G),andthymine(T).核酸堿－腺嘌呤(A)、鳥嘌呤(G)、胸腺嘧啶(T)胞嘧啶(C)(withA.Neumann)14AlbrechtKosseldiscoveredthaTheNobelPrizeinPhysiologyorMedicine1910"inrecognitionofthecontributionstoourknowledgeofcellchemistrymadethroughhisworkonproteins,includingthenucleicsubstances"AlbrechtKosselGermanyUniversityofHeidelberg

Heidelberg,Germany1853-192715TheNobelPrizeinPhysiology核酸的化學(xué)成分–堿基定量研究ErwinChargaff16核酸的化學(xué)成分–堿基定量研究ErwinChargaff1717ErwinChargaff(1905-2002)18ErwinChargaff18Inaddition,chemicalstudiesbyE.ChargaffindicateseveralimportantcluesaboutthestructureofDNA.IntheDNAofallorganisms:

a)Theconcentrationofadenineequalsthatofthymine.

b)Theconcentrationofguanineequalsthatofcytosine.19Inaddition,chemicalstudiesChargaff’Rule

A+G=T+C;

A=T;

G=C;andasalogicalconsequenceofthesethreeequations:

A+C=G+Ti.e.,thesumofthe6-aminocompoundsequalsthatofthe6-oxoderivatives20Chargaff’RuleA+G=T+C;§16.2

核苷Nucleosides核糖、2-脫氧核糖與雜環(huán)堿形成的糖苷21§16.2核苷Nucleosides核糖、2-脫氧核糖2-脫氧腺苷dA2-deoxyadenosine2-脫氧鳥苷dG2-deoxyguanosine組成DNA的核苷222-脫氧腺苷dA2-脫氧鳥苷dG組成DNA的核苷222-脫氧胸苷dT2-deoxythymidine2-脫氧胞苷dC2-deoxycytidine232-脫氧胸苷dT2-脫氧胞苷dC23胞苷(C)Cytidine尿苷(U)Uridine組成RNA的核苷腺苷(A)Adenosine鳥苷(G)Guanosine24胞苷(C)尿苷(U)組成RNA的核苷腺苷(A)鳥苷(G)§16.3

核苷酸NucleotidesThenucleotidesarebuildingblocksofnucleicacids.Nucleosidesarefoundinthecellprimarilyintheirphosphorylatedform.Thesearetermednucleotides.25§16.3核苷酸NucleotidesThenucle2626ribonucleotidesdeoxyribonucleotides2-deoxycytidine5’-monophosphatte27ribonucleotidesdeoxyribonucleAdenosinediphosphate28Adenosinediphosphate28Adenosinetriphosphate

29Adenosinetriphosphate

3030TheRoleofATPThephosphateesterlinkagescanbeviewedtheenergysourceforbiologicalsystems....likeacoiledspring.ThekeychemicalreactionforbioenergeticsistheinterconversionofATPandADP:31TheRoleofATPThephosphate32323'-Azido-3'-Deoxythymidine(AZT)Azidothymidine333'-Azido-3'-Deoxythymidine(AZnucleosidereversetranscriptaseinhibitorAZTisoneofthefewanti-HIVdrugsthatcrosstheblood-brainbarrier.HIVinfectscellsinthebloodstream,thelymphsystem,andthecentralnervoussystem(or"CNS").AZTisbetterthanmostotherdrugsinattackingthevirusintheCNS.Itwasthefirstanti-HIVdrugapprovedforuseintheUnitedStates.34nucleosidereversetranscriptaAZTismanufacturedunderthetradenameRetrovirbyGlaxoSmithKline,andasZidovirbytheIndianmanufacturerCipla.RetrovirwasthefirstdruglicensedtotreatHIVinfection.葛蘭素史克公司35AZTismanufacturedunderthe核酸是核苷酸聚合而成的生物大分子?！?6.4

核酸NucleoicAcidsPolynucleotides生物大分子(III)36核酸是核苷酸聚合而成的生物大分子。§16.4核酸NucOOOO37OOOO373838JD.Waston,F.HCCrick(1953)Waston-CrickModelDNA雙螺旋結(jié)構(gòu)DNA的結(jié)構(gòu)39JD.Waston,F.HCCrick(1953F.H.C.CrickandJ.D.Watson40F.H.C.CrickandJ.D.Watso4141Photo51-Theworldfamousx-raythatestablishedDNAasahelix42Photo51-Theworldfamousx-Nature

171,737-738(1953)MolecularstructureofNucleicAcidsWATSON,J.D.&CRICK,F.H.C.Wewishtosuggestastructureforthesaltofdeoxyribosenucleicacid(D.N.A.).Thisstructurehasnovelfeatureswhichareofconsiderablebiologicalinterest.43Nature171,737-738(1953)MolWearemuchindebtedtoDr.JerryDonohueforconstantadviceandcriticism,especiallyoninteratomicdistances.WehavealsobeenstimulatedbyaknowledgeofthegeneralnatureoftheunpublishedexperimentalresultsandideasofDr.M.H.F.Wilkins,Dr.R.E.Franklinandtheirco-workersatKing'sCollege,London.Oneofus(J.D.W.)hasbeenaidedbyafellowshipfromtheNationalFoundationforInfantileParalysis.Acknowledgements44WearemuchindebtedtoDr.JeTheNobelPrizeinPhysiologyorMedicine1962

F.H.C.Crick

UnitedKingdom

MRCLaboratoryofMolecularBiology

Cambridge,UnitedKingdom1916-2004

J.D.Watson

USAHarvardUniversity

Cambridge,MA,USA1928

M.H.F.Wilkins

UnitedKingdomandNewZealand

LondonUniversity

London,UnitedKingdom1916(inPongaroa,NewZealand)

-2004"fortheirdiscoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial"45TheNobelPrizeinPhysiologyHowever,anotherimportantfigureremains,withoutwhomthediscoverywouldnothavebeenpossible:thebrilliantbutshort-livedRosalindFranklin.46However,anotherimportantfigRosalindFranklin羅莎琳德·富蘭克林

47RosalindFranklin羅莎琳德·富蘭克林47Dr.RosalindFranklin1920-195848Dr.RosalindFranklin1920-194949ThereisprobablynootherwomanscientistwithasmuchcontroversysurroundingherlifeandworkasRosalindFranklin.Franklinwasresponsibleformuchoftheresearchanddiscoveryworkthatledtotheunderstandingofthestructureofdeoxyribonucleicacid,DNA.ThestoryofDNAisataleofcompetitionandintrigue,toldonewayinJamesWatson'sbookTheDoubleHelix,andquiteanotherinAnneSayre'sstudy,RosalindFranklinandDNA.JamesWatson,FrancisCrick,andMauriceWilkinsreceivedaNobelPrize

forthedouble-helixmodelofDNAin1962,fouryearsafterFranklin'sdeathatage37fromovariancancer.50ThereisprobablynootherwomA-TC-G堿基配對Watson-CrickBase-Pairing51A-TC-G堿基配對Watson-CrickBase-Pa52525353545455555656DNA的生物功能載有全部遺傳密碼：DNA所攜帶的全部遺傳信息都記載在DNA所包含的全部核苷酸序列中。DNA雖然只有四種類型的核苷酸，但其相對分子質(zhì)量極大，這四種核苷酸在DNA分子中的排列方式近乎無窮，這就是生物界多樣性的原因。57DNA的生物功能載有全部遺傳密碼：DNA雖然只有四種類型的核585859596060616162626363646465656666

ExposuretoUVlightdamagesDNAandcausesmutations.PhotodimerizationofThymine67

686869697070ThegeneticinformationintheDNAmoleculesdeterminesthecompositionandfunctionoftheproteins.AltmanandCechhavenowmodifiedthisbyshowingthattheRNAmoleculesnotonlytransmitthegeneticinformationbutcanalsofunctionasbiocatalyst.71Thegeneticinformationinthe72727373747475757676聚合酶鏈反應(yīng)PCRPCR技術(shù)是生物醫(yī)學(xué)領(lǐng)域中的重大進展體外核酸擴增技術(shù)PolymeraseChainReactions(PCRs)77聚合酶鏈反應(yīng)PCRPCR技術(shù)是生物醫(yī)學(xué)領(lǐng)域中的重大進展7878797980801983,K.B.Mullis發(fā)明PCR儀，1987年發(fā)表了“SpecificsynthesisofDNAinvitroviaapolymerase-catalyzedchainreaction”，于1993年獲諾貝爾化學(xué)獎。811983,K.B.Mullis發(fā)明PCR儀，19KaryB.Mullis"forcontributionstothedevelopmentsofmethodswithinDNA-basedchemistry"TheNobelPrizeinChemistry1993MichaelSmith82KaryB.Mullis"forcontributio"forhisinventionofthepolymerasechainreaction(PCR)method"KaryB.Mullis

USALaJolla,CA,USA194483"forhisinventionofthepoly"forhisfundamentalcontributionstotheestablishmentofoligonucleotide-based,site-directedmutagenesisanditsdevelopmentforproteinstudies"MichaelSmithCanadaUniversityofBritishColumbia

Vancouver,Canada1932(inBlackpool,UnitedKingdom)-200084"forhisfundamentalcontributTheRoyalSwedishAcademyofSciences

hasdecidedtoawardthe1989NobelPrizeinchemistryjointlytoProfessorSidneyAltman,YaleUniversity,NewHaven,Connecticut,USAandProfessorThomasCech,UniversityofColorado,Boulder,USAfortheirdiscoveryofCatalyticpropertiesofRNA.