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1、BAmericanSocietyforMassSpectrometry,2014J.Am.Soc.MassSpectrom.(2014)25:1098Y1113DOI:10.1007/s13361-013-0808-5FOCUS:MASSSPECTROMETRYANDDNADAMAGE:RESEARCHARTICLEUnderstandingGasPhaseModifierInteractionsinRapidAnalysisbyDifferentialMobility-TandemMassSpectrometry4412,34
2、AmolKafle,StephenL.Coy,BryanM.Wong,AlbertJ.FornaceJr.,JamesJ.Glick,4PaulVouros1DepartmentofChemistryandDepartmentofMaterialsScienceandEngineering,DrexelUniversity,Philadelphia,PA19104,USA2DepartmentofBiochemistryandMolecularandCellBiology,GeorgetownUniversity,Washing
3、ton,DC20057,USA3KingAbdulazizUniversity,CenterofExcellenceinGenomicMedicalResearch,Jeddah21413,SaudiArabia4DepartmentofChemistryandChemicalBiologyandBarnettInstitute,NortheasternUniversity,Boston,MA02115,USAAbstract.Asystematicstudyinvolvingtheuseandoptimizationofgas
4、-phasemodifiersinquantitativedifferentialmobility-massspectrometry(DMS-MS)analysisispresentedusingnucleoside-adductbiomarkersofDNAdamageasanimportantreferencepointforanalysisincomplexmatrices.Commonlyusedpolarproticandpolaraproticmodifiershavebeenscreenedforuseagains
5、ttwodeoxyguanosineadductsofDNA:N-(deoxyguanosin-8-yl)-4-aminobiphenyl(dG-C8-4-ABP)andN-(deoxyguanosin-8-y1)-2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine(dG-C8-PhIP).Particularattentionwaspaidtocompensationvoltage(CoV)shifts,peakshapes,andproductionsignalintensitie
6、swhileoptimizingtheDMS-MSconditions.TheoptimizedparameterswerethenappliedtorapidquantitationoftheDNAadductsincalfthymusDNA.Afteraproteinprecipitationstep,adductlevels6correspondingtolessthanonemodificationin10normalDNAbasesweredetectedusingtheDMS-MSplatform.BasedonDM
7、Sfundamentalsandabinitiothermochemicalresults,weinterpretthecomplexityofDMSmodifierresponsesintermsofthermalactivationandthedevelopmentofsolventshells.Atveryhighbulkgastemperature,modifierdipolemomentmaybethemostimportantfactorinclusterformationandclustergeometry,but
8、atlowertemperatures,multi-neutralclustersareimportantandlesspredictable.ThisworkprovidesausefulprotocolfortargetedDNAadductquantita
