生物活性小分子过亚硝酸根

(421001),46,,:1998202216,1998206201,,,AbstractPeroxynitritewhichproducedinsomebiologicalsystemsisastrongoxidant,andperoxi2dationinducingandnitratingagent.Itcanattackawiderangeofbiologicaltargetsandplayanimportantroleinmanybiologialprocesses.KeywordsPeroxynitrite1929,(Peroxynitrite,ONOO-,)ONOO-ONOO-,ONOO-1990,Beckman[1]ONOO-,ONOO-,,ONOO-1ONOO-,,1987,,,,,BeckmanONOO-:NO+O-2O=NOO-,O-2NO,,ONOO-[2]O-2NO(k=7109mol-1Ls-1),,O-2SOD(k=2109mol-1Ls-1),NO(k107mol-1Ls-1),SODONOO-[3],ONOO-O-2NO,NONO-ONOO-[4]:NO-+O2ONOO-O-2,SOD2ONOO-211,ONOO-ONOOHONOOHcis()trans()73http:ööchina.chemistrymag.org19992©1995-2004TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.,cis2ONOOH[5],5kJömolONOO-cistrans,cis2ONOOHtrans2ONOOHONOO-,pKa618810[6]212ONOOHONOOH,37pH,ONOOH015s[7],,ONOO-,ONOOHONOOH,[8,9][10],ONOOH,,ONOOH,,[HONO2][HO+-NO2][HO-+NO2],ONOOH3,70kJömol,ONOOH3HNO3,ONOOH213ONOO-21311ONOO-ONOOH,ONOOHNO2211[10],,ONOO-ONOOH(ONOOH),ONOO-ONOOH(ONOOH,),ONOOH3HO-+-NO2ONOO-,,[11]21312ONOO-,,,ONOO3,,NO,ONOO-,21313ONOO-,,,[12,13]ONOO-ONOOHpH,,ArAr,,3ONOO-311ONOO-,,ONOO-:,,,DNA[14][15]312SODSODNOO-2ONOO-,NO,ONOO-,SODONOO-ONOO-,,SOD,ONOO-[13]313ECONOO-,ONOO-,ONOO-[16]ONOO-EC,EC8319992http:öö©1995-2004TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.314ONOO-ONOO-[12,13],ONOO-315,ONOO-ONOO-,ONOO-ONOO-,,,C[17]ONOO-ONOO-ONOOCO-2,ONOOCO-2ONOO-,ONOO-,NO2CO-3,4ONOO-411NONO,NONOONOO-,412ONOO-NOO-2NO,O-2,,ONOO-,ONOO-NOO-2O-2O-2,Fenton,O-2,SODO-2O-2ONOO-[11],SODO-2413ONOO-,ONOO-,ONOO-,[18]ONOO-ONOO-414ONOO-NOO-2ONOO-[19],NOO-2ONOO-415ONOO-ONOO-,,ONOO-,ONOO-ONOO-DNA,[20],5ONOO-,ONOO-,ONOO-,,ONOO-ONOO-ONOO-93http:ööchina.chemistrymag.org19992©1995-2004TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.,ONOO-,ONOO-,,ONOO-,,,ONOO-[1]BeckmanJS,BeckmanWT,ChenJetal.Aparenthydroxylradicalproductionbyperoxynitrite:implicationsforendothelialinjuryfromnitricoxideandsuperoxide.Proc.Natl.Acad.Sci.USA,1990,87:16201624.[2],,,.NOO-2ONOO-.(C),1996,26:406413.[3]HuicRE,PadmajaS.ThereactionofNOwithsuperoxide.FreeRadicalRes.Commun.,1993,18:195199.[4]SinghRJ,HoggN,KalyanaramanB.Intractionofnitricoxidewithphotoexciedrosbengal:evidenceforone2electronreduc2tionofnitricoxidetonitroxylanion.ArchBiochem.Biophys.,1995,324:367373.[5]McGrathMP,RowlandFS.DeterminationofthebarrierstointernalrotationinONOOX(X=H,Cl)andcharacterizationoftheminimumenergyconformers.J.Phys.Chem.,1994,98:10611067.[6]CrowJP,SpruellC,ChemJetal.OnthepH2dependentyieldofhydroxylradicalproductsfromperoxynitrite.FreeRadicalBiol.Med.1994,16:331338.[7]PryorWA,JinX,squaeritoGL.One2andtwo2electronoxidationsofmethioninebyperoxynitrite.Proc.Natl.Acad.Sci.USA,1994,91:11173211177.[8]Vasquez2VivarJ,SantosAM,JunqueiraVBCetal.Peroxynitrite2mediatedformationoffreeradicalsinhumanplasma:EPEdetectionofascorbyl,abbumin2thiylanduricacid2derivedfreeradicals.Biochem.J.,1996,314:869876.[9],,,..,1996,24:258261.[10]KoppenolWH,MorenoJJ,PryorWAetal.Peroxynitrite,acloakedoxidantformedbynitricoxideandsuperoxide.Chem.Res.Toxicol.,1992,5:834842.[11]RadiR,BeckmanJS,BushKMetal.Peroxynitriteoxidationofsulfhydryls:thecytotoxicpotentialofsuperoxideandnitricoxide.J.Biol.Chem.,1991,266:42444250.[12],,,..,1997,24:450453.[13]BeckmanJS,IschiropoulosH,ZhuLetal.Kineticsofsuperoxidedismutase2andiron2catalyzednitrationofphenolicsbyperoxynitrite.ArchBiochem.Biophys.,1992,298:438445.[14]YoshieY,OhshimaH.NitricoxidesyneristicallyenhancesDNAstrandbreakageinducedbypolyhydroxyaromaticcom2pounds,butinhibitsthatinducedbytheFentonreaction.ArchBiochem.Biophys.,1997,342:1321.[15]GadelhaFR,ThomsonL,FagianMMetal.Ca2+-independentpermeabilizationoftheinnermitochondrialmembranebyperoxyitriteismediatedbymembraneproteinthiolcross2linkingandlipidperoxidation.ArchBiochem.Biophys.,1997,345:243250.[16]KarouiH,HoggN,FrejavilleCetal.Characterizationofsulfur2centeredradicalintermediatesformedduringtheoxidationofthiolsandsulfitebyperoxynitrite.ESR2spintrappingandoxygenuptakestudies.J.Biol.Chem.,1996,271:60006009.[17]LemercierJN,PadmajaS,CuetoRetal.Carbondioxidemodulationofhydroxylationandnitrationofphenolbyperoxyni2trite.ArchBiochem.Biophys.,1997,345:160170.[18]ZingarelliB,OpConnorM,WorgHetal.Peroxynitrite2mediatedDNAstrandbreakageactivatespoly2adenosinediphosphateribosylsynthetaseandcausescellularenergydepletioninmacrophagesstimulatedwithbacteriallipopolysaccharide.J.Im2munol.,1996,156:350358.[19]TroyCM,DerossiD,ProchiantzAetal.DownregulationofCuöZnsuperoxidedismutaseleadstocelldeathviathenitricox2ide2peroxynitritepathway.J.Neurosci.,1996,16:253261.[20]BerlettBS,FriguetB,YimMBetal.Peroxynitrite2mediatednitrationoftyrosineresiduesinEscherichiacoliglutaminesyn2thetasemimicsadenylglation:relevancetosignaltransduction.Proc.Natl.Acad.Sci.USA,1996,93:17761780.0419992http:öö©1995-2004TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.