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1、ThenovelfeatureofthestructureisthemannerinwhichthetwochainsareheldThenovelfeatureofthestructureisthemannerinwhichthetwochainsareheld1953年沃森和克里克发现DNA双螺旋结构发表在Nature上的论文2April1953MOLECULARSTRUCTUREOFNUCLEICACIDSAStructureforDeoxyriboseNucleicAcidThis看再口吐ispirelydiamiTimat-ir.TWttwribbonssymbcliae-tlivt
2、w*hak由tsarandtjicliori-zontlrodstSiepaireofhaacaboltingMicchintnscth,flr.Tlieverticallinemarkthuftbnesixi6Wewishtosuggestastructureforthesaltofdeoxyribosenucleicacid(D.N.A.).Thisstructurehasnovelfeatureswhichareofconsiderablebiologicalinterest.AstructurefornucleicacidhasalreadybeenproposedbyPaulinga
3、ndCorey(1).Theykindlymadetheirmanuscriptavailabletousinadvanceofpublication.Theirmodelconsistsofthreeintertwinedchains,withthephosphatesnearthefibreaxis,andthebasesontheoutside.Inouropinion,thisstructureisunsatisfactoryfortworeasons:(1)WebelievethatthematerialwhichgivestheX-raydiagramsisthesalt,nott
4、hefreeacid.Withouttheacidichydrogenatomsitisnotclearwhatforceswouldholdthestructuretogether,especiallyasthenegativelychargedphosphatesneartheaxiswillrepeleachother.(2)SomeofthevanderWaalsdistancesappeartobetoosmall.Anotherthree-chainstructurehasalsobeensuggestedbyFraser(inthepress).Inhismodelthephos
5、phatesareontheoutsideandthebasesontheinside,linkedtogetherbyhydrogenbonds.Thisstructureasdescribedisratherill-defined,andforthisreasonweshallnotcommentonit.Wewishtoputforwardaradicallydifferentstructureforthesaltofdeoxyribosenucleicacid.Thisstructurehastwohelicalchainseachcoiledroundthesameaxis(seed
6、iagram).Wehavemadetheusualchemicalassumptions,namely,thateachchainconsistsofphosphatediestergroupsjoiningB-D-deoxyribofuranoseresidueswith3,5linkages.Thetwochains(butnottheirbases)arerelatedbyadyadperpendiculartothefibreaxis.Bothchainsfollowright-handedhelices,butowingtothedyadthesequencesoftheatoms
7、inthetwochainsruninoppositedirections.EachchainlooselyresemblesFurbergs2modelNo.1;thatis,thebasesareontheinsideofthehelixandthephosphatesontheoutside.TheconfigurationofthesugarandtheatomsnearitisclosetoFurbergsstandardconfiguration,thesugarbeingroughlyperpendiculartotheattachedbase.Thereisaresidueon
8、eachevery3.4A.inthez-direction.Wehaveassumedanangleof36betweenadjacentresiduesinthesamechain,sothatthestructurerepeatsafter10residuesoneachchain,thatis,after34A.Thedistanceofaphosphorusatomfromthefibreaxisis10A.Asthephosphatesareontheoutside,cationshaveeasyaccesstothem.Thestructureisanopenone,andits
9、watercontentisratherhigh.Atlowerwatercontentswewouldexpectthebasestotiltsothatthestructurecouldbecomemorecompact.Fulldetailsofthestructure,includingtheconditionsassumedinbuildingit,togetherFulldetailsofthestructure,includingtheconditionsassumedinbuildingit,togethertogetherbythepurineandpyrimidinebas
10、es.Theplanesofthebasesareperpendiculartothefibreaxis.Thearejoinedtogetherinpairs,asinglebasefromtheotherchain,sothatthetwoliesidebysidewithidenticalz-co-ordinates.Oneofthepairmustbeapurineandtheotherapyrimidineforbondingtooccur.Thehydrogenbondsaremadeasfollows:purineposition1topyrimidineposition1;pu
11、rineposition6topyrimidineposition6.Ifitisassumedthatthebasesonlyoccurinthestructureinthemostplausibletautomericforms(thatis,withtheketoratherthantheenolconfigurations)itisfoundthatonlyspecificpairsofbasescanbondtogether.Thesepairsare:adenine(purine)withthymine(pyrimidine),andguanine(purine)withcytos
12、ine(pyrimidine).Inotherwords,ifanadenineformsonememberofapair,oneitherchain,thenontheseassumptionstheothermembermustbethymine;similarlyforguanineandcytosine.Thesequenceofbasesonasinglechaindoesnotappeartoberestrictedinanyway.However,ifonlyspecificpairsofbasescanbeformed,itfollowsthatifthesequenceofb
13、asesononechainisgiven,thenthesequenceontheotherchainisautomaticallydetermined.Ithasbeenfoundexperimentally(3,4)thattheratiooftheamountsofadeninetothymine,andtherationofguaninetocytosine,arealwaysberyclosetounityfordeoxyribosenucleicacid.Itisprobablyimpossibletobuildthisstructurewitharibosesugarinpla
14、ceofthedeoxyribose,astheextraoxygenatomwouldmaketoocloseavanderWaalscontact.ThepreviouslypublishedX-raydata(5,6)ondeoxyribosenucleicacidareinsufficientforarigoroustestofourstructure.Sofaraswecantell,itisroughlycompatiblewiththeexperimentaldata,butitmustberegardedasunproveduntilithasbeencheckedagains
15、tmoreexactresults.Someofthesearegiveninthefollowingcommunications.Wewerenotawareofthedetailsoftheresultspresentedtherewhenwedevisedourstructure,whichrestsmainlythoughnotentirelyonpublishedexperimentaldataandstereochemicalarguments.Ithasnotescapedournoticethatthespecificpairingwehavepostulatedimmedia
16、telysuggestsapossiblecopyingmechanismforthegeneticmaterial.withasetofco-ordinatesfortheatoms,willbepublishedelsewhere.WearemuchindebtedtoDr.JerryDonohueforconstantadviceandcriticism,especiallyoninteratomicdistances.Wehavealsobeenstimulatedbyaknowledgeofthegeneralnatureoftheunpublishedexperimentalres
17、ultsandideasofDr.M.H.F.Wilkins,Dr.R.E.Franklinandtheirco-workersatKingsCollege,London.Oneofus(J.D.W.)hasbeenaidedbyafellowshipfromtheNationalFoundationforInfantileParalysis.J.D.WATSONF.H.C.CRICKMedicalResearchCouncilUnitfortheStudyofMolecularStructureofBiologicalSystems,CavendishLaboratory,Cambridge
18、.April2.Pauling,L.,andCorey,R.B.,Nature,171,346(1953);Proc.U.S.Nat.Acad.Sci.,39,84(1953).Furberg,S.,ActaChem.Scand.,6,634(1952).Chargaff,E.,forreferencesseeZamenhof,S.,Brawerman,G.,andChargaff,E.,Biochim.etBiophys.Acta,9,402(1952).Wyatt,G.R.,J.Gen.Physiol.,36,201(1952).Astbury,W.T.,Symp.Soc.Exp.Biol
19、.1,NucleicAcid,66(Camb.Univ.Press,1947).Wilkins,M.H.F.,andRandall,J.T.,Biochim.etBiophys.Acta,10,192(1953).VOL171,page737,1953Theyear1953couldbesaidtomark,inbiologyatleast,theendofhistory.HereisJamesWatsonandFrancisCrickspaperonthestructureofDNA,whichusheredinthenewerawiththecelebratedunderstatement
20、neartheend.(aspublishedinNATUREmagazine)我们拟提出脱氧核糖核酸(DNA)盐的一种结构。这种结构的崭新特点具有重要的生物学意义。鲍林和考瑞曾提出过一个核酸结构。他们在发表这一结构之前,欣然将手稿送给我们一阅。他们的模型包含磷酸接近纤维袖,碱基在外周的三条多核苷酸链。我们觉得这样的结构是不够满意的,其理由有二:(1)我们认为进行过X射线衍射分析的样品是DNA的盐而不是游离的酸。没有酸性氢原子,接近轴心并带负电的磷酸会相互排斥。在这样的条件下,究竟是什么力量把这种结构维系在一起,尚不清楚。(2)范德瓦尔力距似显太小。弗雷泽曾提出过另外一种三条多核苷酸链的结构(将出版)。在他的模型中,磷酸在外边,碱基在内部,并由氢键维系着。他描述的这种结构也不够完善,因此,我们将不予评论。我们拟提出一个完全不同的脱氧核糖核酸盐的结构。该结构具有绕同一轴心旋转的两条螺旋链(见图)。根据化学常识我们假定,每条链包括联结
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