“RNA世界”之父《Science》遗世之作破解生命起源之谜
- 格式：pdf
- 大小：480.85 KB
- 文档页数：6
DOI: 10.1126/science.1174577, 73 (2009);325 Science et al.Yasuyuki UraSelf-Assembling Sequence-Adaptive Peptide Nucleic Acids This copy is for your personal, non-commercial use only. clicking here.colleagues, clients, or customers by , you can order high-quality copies for yourIf you wish to distribute this article to others here.following the guidelines can be obtained byPermission to republish or repurpose articles or portions of articles
): August 13, 2012 www.sciencemag.org (this information is current as ofThe following resources related to this article are available online at
http://www.sciencemag.org/content/325/5936/73.full.htmlversion of this article at: including high-resolution figures, can be found in the onlineUpdated information and services,
http://www.sciencemag.org/content/suppl/2009/06/11/1174577.DC1.html can be found at: Supporting Online Material http://www.sciencemag.org/content/325/5936/73.full.html#ref-list-1, 1 of which can be accessed free:cites 30 articlesThis article 11 article(s) on the ISI Web of Sciencecited by This article has been http://www.sciencemag.org/content/325/5936/73.full.html#related-urls2 articles hosted by HighWire Press; see:cited by This article has been
http://www.sciencemag.org/cgi/collection/chemistryChemistrysubject collections:This article appears in the following
registered trademark of AAAS. is aScience2009 by the American Association for the Advancement of Science; all rights reserved. The title CopyrightAmerican Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by theScience
on August 13, 2012www.sciencemag.org
Downloaded from Self-AssemblingSequence-AdaptivePeptideNucleicAcidsYasuyukiUra,1JohnM.Beierle,1LukeJ.Leman,1LeslieE.Orgel,2M.RezaGhadiri1*Severalclassesofnucleicacidanalogshavebeenreported,butnosyntheticinformationalpolymerhasyetprovenresponsivetoselectionpressuresunderenzyme-freeconditions.Here,weintroduceanoligomerfamilythatefficientlyself-assemblesbymeansofreversiblecovalentanchoringofnucleobaserecognitionunitsontosimpleoligo-dipeptidebackbones[thioesterpeptidenucleicacids(tPNAs)]andundergoesdynamicsequencemodificationinresponsetochangingtemplatesinsolution.Theoligomersspecificallyself-pairwithcomplementarytPNAstrandsandcross-pairwithRNAandDNAinWatson-Crickfashion.Thus,tPNAcombinesbase-pairinginteractionswiththeside-chainfunctionalitiesoftypicalpeptidesandproteins.Thesecharacteristicsmightproveadvantageousforthedesignorselectionofcatalyticconstructsorbiomaterialsthatarecapableofdynamicsequencerepairandadaptation.
Althoughseveralclassesofnucleicacid
analogshavebeenreported(1–6),nearlyallpreviouslypostulatedmechanismsforconstructingnucleicacidoligomersinvokeanirreversiblecovalentbackboneassemblyofnucleobase-containingmonomersorfragments.Weenvisionedthatafundamentallydifferentoligo-merassemblymechanismrelyingondynamiccovalentchemistry(7–19)couldinvolvetherevers-ibleanchoringofnucleobaseunitsontoindepen-dentlypreformedbackbonestructures(20).Inthepresentstudy,weinvestigateanoligomersystembasedonasimplerepeatingdipeptidebackbonemotif(1).Thedesignfeaturescysteineresiduesatalternatingaminoacidpositionstoprovidethean-chorforreversibletetheringofnucleobasethioestermonomersfromsolutionviatransthioesterifica-tionreactions.Althoughanumberofreversiblecovalentreactionscouldbeemployedfornucleo-baseanchoring,thioesterexchangewaschosenforitschemoselectiveandrelativelyfastreactionkinetics,prebioticrelevance,andbecauseital-lowedtheemploymentofanaturalaminoacid(Cys)foranchoring[seefig.S7formolecularmodelssupportingthestructuralcompatibilityofthioesterpeptidenucleicacid(tPNA)forinter-strandbasepairingwithcomplementaryoligonu-cleotides].Avarietyofaminoacidresiduescanbeusedattheflankingpositionsofthebackbone(Glu,Asp,Arg,andGlyresidueswereemployedhere)toprovidetheappropriatespacingbetweenCysresidues(1),improvedaqueoussolubility,backboneflexibility,and/orelectrostaticproper-tiesforimprovedinteractionswithnucleicacids(Fig.1).Becauseourstudiesexperimentallyestab-lishaprocessinvolvingpeptidesastheintegralcomponentforthespontaneousassemblyofinfor-mationaloligomers,itistantalizingtospeculateaboutthepossibleinterdependenceofpeptidesandnucleicacidsattheadventofprimordial(pre-RNAWorld)geneticsystems(21–24).Weinitiallyinvestigatedtheassemblyoftheadeninethioester(500mM)(seefig.S1fornucleobasesyntheses)onto(Glu-Cys)10peptide1(100mM)(25).Becausepeptide1contains10Cysresidues,thenucleobasethioesterwaspresentinjust0.5equivalentsrelativetoCysinthisreac-tion.Theanchoringreactionwasrapidandef-ficient,generatingabell-shapeddistributionofsubstitutedpeptideswithin30min,asdeterminedbymatrix-assistedlaserdesoption/ionization–time-of-flightmassspectrometry(MALDI-TOFMS)(Fig.2A).WhenthenucleobasethioesterwaspresentinatwofoldexcessorhigherratiorelativetoCys,thefullysubstituted10-merand9-mersubstitutedtPNAstrandspredominatedafter30min(Fig.2A).Productdistributionsdidnotchangewhenanalyzedafterlongerreactiontimes.Theseresultsareconsistentwithreportsindicatingthatequilibriumindynamiccombina-
