姓名：杨科武性别：男
部门：有机化学与化学生物学学部
职称：教授
邮箱：kwyang@nwu.edu.cn电话：Phone/Fax:+86/0-29-8830-2429(O)
研究方向：ChemicalBiology,Metalloenzyme&AntibioticResistance,ProteinChip,Biopharmaceuticals

简介

BIOGRAPHY

ProfessorYangreceivedhisPhDinchemistryin1994fromLanzhouInstituteofChemicalPhysics,ChineseAcademyofSciences,workingunderthesupervisionofProf.YuanqiYin.HespentthefollowingtwoyearsasapostdoctoralfellowandthenjoinedthefacultyatFudanUniversityasanassociateprofessorin1996.HepursuedNationalInstitutesofHealth'sresearchprojectsatMiamiUniversityworkinginthelabofprofessorMichaelCrowderfrom1998to2004,andfollowedservicedGirindusAmericaInc.attheMedicinalChemistryDepartmentasaseniorscientisttomastermindtheresearchanddevelopmentprojectsfromProcterandGambleandAventisPharmaceuticals.Dr.YangjoinedthefacultyatNorthwestUniversityasaprofessorandleadinginvestigatorinchemicalbiologyin2007.HeisamemberofSIGMAXI,TheScientificResearchSociety.

RESEARCHINTERESTS

TheinterestsofourChemicalBiologyLab(CBL)focusonimportantbiomedicaltargets.Weareinterestedinusingthetoolsofproteinchemistry,organicsynthesis,molecularbiologyandbiophysicstodevelopclinically-usefulcompoundsforthediagnosesandtreatmentofthebiomedicaltargetsincludingantibioticresistantbacteria.WeareparticularlyinterestedintakingamultidisciplinaryapproachtodevelopaProteinChiptechnologyforhighthroughputscreeningoftheantibioticresistantbacteria.Researchersinthegroupworkattheinterfaceofchemistry,biology,medicineandpharmaceuticals.Wearecurrentlyengagingthefollowingprojects.

1.Metallo-β-lactamases(MβLs)

Themostcommonprescribedantibioticsareβ-lactamcompoundssuchaspenicillins,cephalosporinsandcarbapenems.Theoveruseofantibioticsintheclinicalsettinghasresultedinalargenumberofbacteriawhichareresistanttoalmostallantibiotics.Themostcommonwayforbacteriatobecomeresistanttoβ-lactamantibioticsistoproducethemetallo-β-lactamases(MβLs),whichhydrolyzealmostallβ-lactamantibiotics.Wearecurrentlyconductinginhibitorsynthesis,spectroscopicandmechanisticcharacterizationofinteractionbetweeninhibitorsandMβLsbyNMR,EPR,EXAFSandRFQinanattempttodevelopbroad-spectruminhibitorsoftheMβLsforcombatingantibioticresistance.

2.D-ala-D-ala-DipeptidaseVanX

VancomycininhibitsbacterialcellwallsynthesisbybindingtotheD-ala-D-alanineendofthepentapeptideviafivehydrogenbonds,therebypreventingcross-linkingofthepentapeptidestoformthenormalbacterialpeptidoglycanlayer.VanXhydrolyzesalmostallofD-ala-D-alanyldipeptidesofthepentapeptidessothatvancomycinlosesthetargets.Clearly,toproducetight-bindinginhibitorofVanXisaneffectivewaytocombatvancomycinresistanceinbacteria.Towardsthisgoal,weareimplementingrationalstrategytodesign,synthesizeandevaluateinhibitorsoftheVanX,toinvestigatestructure-activityrelationship(SAR),whichisusedforguidingdesignofnewdrugs.

3.Glyoxalase-IIIsozymes

BiochemicalstudiesonglyoxalasesystemhaveimplicatedGlyoxalase-II(GLX-II)isindetoxificationofcytotoxic2-oxoaldehydesfromthecellandtheinhibitorsofGLX-IIcanstopgrowthoftumors,becausethetumorshavenowaytoremovethetoxicbyproducts.InanefforttoprobeinhibitionofGLX-II,wedesign,synthesizeandevaluateglutathionederivativesasinhibitors,andinvestigatedwhichsubstitutesontheinhibitorareessentialfortightbinding,andwhetherhydrophobicinteractionscontributetothetightbindingoftheinhibitors.Thisstudyistargetedfordevelopmentofpotentialantitumorreagents.


4.ProteinChip&SmallMoleculeChip

Basedonourunderstandingandinvestidatingtothestructure,mechanism,functionandinhibitionofthemetalloenzymesinantibioticresistantbacteriaandtheirreactionwithspecificsubstrateandinhibitor,wearetakingamultidisciplinaryapproachtodevelopaspecificProteinChiptechnologyforidentifyinganddetectingtheantibioticresistantbacteriasuchasMycobacteriumtuberculosisandStaphylococcusaureus,andtodevelopaspecificsmallMoleculeChiptechnologyforhighthroughputscreeningofantibacterialreagents.




MAINPROJECTSACCOMPLISHED

>Inhibitionstudiesofmetallo-β-lactamasesastargetproteinsofantibioticresistance(**,640-2013-8804),NSFC-SwedishResearchCounciljointresearchprogram,PI
>Broad-spectruminhibitionstuidesonantibioticresistantbacteria(**),NSFC,PI
>Vancomycinresistance:structureoptimizationandactivityofVanXinhibitor(**),NSFC,PI
>ForeignExpertfundofNationalPersonnelMinistry(**),PI
>DoctoralFundoftheMinistryofEducation(**5),PI
>KeyFundforInternationalCooperationofShaanxiProvince(2014KW23-03),PI
>KeyFundforInternationalCooperationofShaanxiProvince(2010KW-16),PI
>NaturalScienceFundofShaanxiProvince(2009JM2002),PI
>Developmentofprodrugsforthetreatmentofosteoporosis,Procter&Gamble,PI
>Syntheticdevelopmentofanti-herpescompounds,AventisPharmaceuticals,PI
>Characterizationofmetallo-β-lactamases,NationalInstitutesofHealth(NIH),Co-PI
>Characterizationofmetallo-β-lactamasesfromX.maltophilia,NationalInstitutesofHealth(NIH),Co-PI
>InhibitionStudiesond-ala-d-aladipeptidaseVanX,NationalScienceFundation(NSF),Co-PI
>StudiesonglyoxalaseIIinarabidopsisthaliana,NationalScienceFundation(NSF),Co-PI


PHOTOS-CHEMICALBIOLOGYLAB
ThemembersofChemicalBiologyLab

ProteinCharacterization.pdf

MolecularBiology.pdf

ProteinPreparation2.pdf

ProteinPurification.pdf

ChemicalSynthesis.pdf

CollaborationwithMU(US),CSPU(US)&UG(Swedish)
ProfessorCrowdervisitedCBLinAugust2010












冯雷/LeiFeng:PhD,1982-kidd@163.com
刘成程/Cheng-ChengLiu:PhD,stone9947@sina.com.cn












肖建敏/Jian-MinXiao:Graduate,xiaomin0622@126.com













翟乐/LeZhai:PhD,zhaile1986@126.com
周立生/Li-ShengZhou:Graduate,zhoulishengandy@163.com




















石莹/YingShi:Graduate,**@qq.com
张亦琳/Yi-LinZhang:PhD,yilin_190@126.com












周亚俊/Ya-JunZhou:Graduate,zhouyajun@foxmail.com
杨少康/Shao-KangYang:Graduate,yskmusic@126.com












向阳/YangXiang:Graduate,x**@163.com
文婧/JingWen:Undergraduate,xida_wenjing@163.com










　
















SELECTEDPUBLICATIONS

YLZhang,KWYang*,YJZhou,AELaCuran,POelschlaeger,MWCrowder,“Diaryl-substitutedazolylthioacetamides:inhibitordiscoveryofNewDelhimetallo-β-lactamase-1(NDM-1)”,ChemMedChem.doi:10.1002/cmdc.**

XYang,YJZhou,PHe,YHGuo,CJLiu,andKWYang*,“ActivationfreeenergyofZn(II),Co(II)bindingtometallo-β-lactamaseImiS”,Chi.Chem.Lett.doi:10.1016/j.cclet.2014.06.024.

JMXiao,LFeng,LSZhou,HZGao,YLZhang,KWYang*,“Novelfluorescentcephalosporins:synthesis,antimicrobialactivityandphotodynamicinactivationofantibioticresistantbacteria”,Eur.J.Med.Chem.2013,59,150-159.

HZGao,KWYang*,XLWu,JYLiu,LFeng,JMXiao,LSZhou,CJia,ZShi,“Novelconjugationofnorvancomycin-fluoresceinforphotodynamicinactivationofBacillussubtilis”,BioconjugateChem.2011,22,2217?2221.

CCLiu,LSZhou,JYLiu,JMXiao,HZGao,KWYang*,“Photoinactivationofvancomycin-resistantEnterococciandBacillussubtilisbynovelconjugatenorvancomycin-rhodamineB”,NewJ.Chem.2013,37,575-580.

LFeng,KWYang*,SKYang,MAitha,AELaCuran,POelschlaeger,MWCrowder*,“Newβ-phospholactamasacarbapenemtransitionstateanalog:synthesisofabroad-spectruminhibitorofmetallo-β-lactamases”,Bioorg.Med.Chem.Lett.2013,23,5855–5859.

LSZhou,KWYang*,LFeng,JMXiao,CCLiu,YLZhang,MWCrowder*,“Novelfluorescentrisedronates:synthesis,photodynamicinactivationandimagingofBacillussubtilis”,Bioorg.Med.Chem.Lett.2013,23,949-954.

YLZhang,JMXiao,JLFeng,KWYang*,LFeng,LSZhou,MWCrowder*,“AnovelfluorogenicsubstratefordinuclearZn(II)-containingmetallo-β-lactamases”,Bioorg.Med.Chem.Lett.2013,23,1676-1679.

YShi,LFeng,QYang,YJZhou,KWYang*,“Thermokineticevaluationofpyrrolidinedicarboxylicacidinhibitingcefalexinhydrolysiswithmetallo-β-lactamaseL1fromStenotrophomonasmaltophilia”,ThermochimicaActa,2013,563,46-50.

LZhai,LSZhou,CCLiu,YShi,YJZhou,KWYang*,“Determinationofthermodynamicparametersofbenzylpenicillinhydrolysisbymetallo-β-lactamaseCcrAfromBacteroidesfragilis”,ThermochimicaActa,2013,556,54-57.

CCLiu,XBZhao,KWYang*,KZXu,LZhai,XYang,HZGao,“ExploringantibioticresistancebasedonenzymehydrolysisbymicrocalorimetryIV:determinationofthermokineticparametersofd-ala-d-alahydrolysiswithdipeptidaseVanX”,J.Therm.Anal.Calorim.2013,111(3),1663-1667.

LZhai,KWYang*,CCLiu,KZXu,XYang,HZGao,YShi,LFeng,CJia,LSZhou,JMXiao,“ExploringantibioticresistancebasedonenzymehydrolsisbymicrocalorimetryⅢ:determinationofthermokineticparametersofcefazolinhydrolysiswithmetallo-β-lactamaseCcrA”,J.Therm.Anal.Calorim.2013,111(3),1657-1661.

CCLiu,LZhai,YShi,KWYang*,“Purificationofmetallo-β-lactamaseCcrAfromBacteroidesfragiliswithsalting-outmethod”,Braz.Arch.Biol.Technol.2013,56(5),811-816.

LFeng,KWYang*,LSZhou,JMXiao,XYang,LZhai,YLZhang,MWCrowder*,“N-heterocyclicdicarboxylicacids:broad-spectruminhibitorsofmetallo-β-lactamaseswithco-antibacterialeffectagainstantibiotic-resistantbacteria”,Bioorg.Med.Chem.Lett.2012,22,5185–5189.

CJia,KWYang*,CCLiu,LFeng,JMXiao,LSZhou,YLZhang,“Synthesis,characterizationandactivityofnewphosphonatedipeptidesaspotentialinhibitorsofVanX”,Bioorg.Med.Chem.Lett.2012,22,482-484.

LZhai,KWYang*,CCLiu,HZGao,XYang,YShi,JWen,“Thermokineticcharacterizationofimipenemhydrolysiswithmetallo-β-lactamaseCcrAfromBacteroidesfragilis”,ThermochimicaActa.2012,539,67-70.

XYang,LFeng,KZXu,HZGao,CJia,CCLiu,JMXiao,LZhai,LSZhou,KWYang*,“ExploringantibioticresistantmechanismbymicrocalorimetryII:determinationofthermokineticparametersofimipenemhydrolysiswithmetallo-β-lactamaseImiS”,J.Therm.Anal.Calorim.2012,110,945-948.

HZGao,QYang,XYYan,ZJWang,JLFeng,XYang,SLGao,LFeng,XCheng,CJia,KWYang*,“DeterminationofthermodynamiccarametersofpenicillinGhydrolysiscatalyzedbymetallo-β-lactamaseL1fromStenotrophomonasmaltophilia”,J.Therm.Anal.Calorim.2012,107,321-324.

KWYang*,XCheng,CZhao,CCLiu,CJia,LFeng,JMXiao,LSZhou,HZGao,XYang,LZhai,“SynthesisandactivitystudyofphosphonamidatedipeptidesaspotentialinhibitorsofVanX”,Bioorg.Med.Chem.Lett.2011,21,7224-7227.

HZGaoandKWYang*,“Antibioticresistanceinsuperbugs:researchprogressofthemetallo-β-lactamases”,Chin.Pharm.J.2011,47(5),325-330.

XBZhao,ZHZhang,XXYanandKWYang*,“Researchprocessandapplicationofbisphosphonatedrugs”,Chin.J.Osteoporos,2011,17(10),65-69.

YanXY,GaoHZ,FengJL,YangX,FengL,ChengX,JiaC,YangKW*,"Wild-typeandCo(II)substitutedmetallo-β-lactamaseL1:spectroscopiccharacterizationandkineticstudiesofcatalyzingantibiotichydrolysis",Chin.J.Antibiot.2011,36(5),388-393.

FengJL,YangX,YanXY,GaoHZ,FengL,ChengX,JiaC,WuD,YangKW*,"Expression,purificationofImiSandkineticstudiesonhydrolysisofthreetypeofβ-lactamantibioticscatalyzedbyImiS",Chin.J.Antibiot.2011,36(3),197-200.

A.L.Costello,G.Periyannan,K.W.Yang,M.W.Crowder*,D.L.Tierney,“SiteselectivebindingofZn(II)tometallo-β-lactamaseL1fromStenotrophomonasmaltophilia”,J.Biol.Inorg.Chem.2006,11(3),351-358.

A.L.Costello,N.P.Sharma,K.W.Yang,M.W.Crowder*,D.L.Tierney,“X-rayabsorptionspectroscopyofthezinc-bindingsitesintheclassB2metallo-β-lactamaseImiSfromAeromonasveroniibv.sobria”,Biochemistry,2006,45,13650-13658.

G.R.Periyannan,A.L.Costello,D.L.Tierney,K.W.Yang,B.Bennett,M.W.Crowder*,“Sequentialbindingofcobalt(II)tometallo-β-lactamaseCcrA”,Biochemistry,2006,45,1313-1320.

N.P.Sharma,C.Hajdin,S.Chandrasekar,B.Bennett,K.W.Yang,M.W.Crowder*,“MechanisticstudiesonthemononuclearZn(II)-containingmetallo-β-lactamaseImiSfromAeromonassobria”,Biochemistry,2006,45,10729-10738.

P.A.Crawford,K.W.Yang,N.Sharma,B.Bennett,M.W.Crowder*,"SpectroscopicstudiesonCo(II)-substitutedmetallo-β-lactamaseImiSfromAeromonasveroniibv.sobria",Biochemistry,2005,44,5168-5176.

K.W.Yang,F.C.Golich,T.K.Sigdel,M.W.Crowder*,“Phosphinate,sulfonateandsulfonamidatedipeptidesaspotentialinhibitorsofaminopeptidaseN”,Bioorg.Med.Chem.Lett.2005,15,5150-5153.

G.P.Marasinghe,I.M.Sander,B.Bennett,G.Periyannan,K.W.Yang,C.A.Makaroff,M.W.Crowder*,“StructuralstudiesonamitochondrialglyoxalaseII”,J.Biol.Chem.2005,280,40668-40675.

K.W.YangandM.W.Crowder*,"Amethodforremovingethylenediaminetetraaceticacidfromapo-proteins",Anal.Biochem.2004,329,342-344.

K.W.Yang,D.N.Sobieski,A.L.Carenbauer,P.A.Crawford,C.A.Makaroff,M.W.Crowder*,“ExplainingtheinhibitionofglyoxalaseIIby9-fluorenylmethoxycarbonyl-protectedglutathionederivatives”,Arch.Biochem.Biophys.2003,414,271-278.

M.W.Crowder*,K.W.Yang,A.L.Carenbauer,G.Periyannan,M.E.Seifert,N.E.Rude,T.R.Walsh,“TheproblemofasolventexposabledisulfidewhenpreparingCo(II)-substitutedmetallo-β-lactamaseL1fromStenotrophomonasmaltophilia”,J.Biol.Inorg.Chem.2001,6,91-99.

K.W.Yang,J.J.Brandt,L.L.Chatwood,M.W.Crowder*,“PhosphonamidateandphosphothioatedipeptidesaspotentialinhibitorsofVanX”,Bioorg.Med.Chem.Lett.2000,10,1085-1087.

K.W.Yang,M.W.Crowder*,“Inhibitionstudiesonthemetallo-β-lactamaseL1romStenotrophomonasmaltophilia”,Arch.Biochem.Biophys.1999,368,1-6.

J.J.Brandt,L.L.Chatwood,K.W.Yang,M.W.Crowder*,“ContinuousassayforVanX,theD-ala-D-aladipeptidaserequiredforhigh-levelvancomycinresistance”,Anal.Biochem.1999,272,94-99.

M.W.Crowder*,S.McMannus-Munoz,A.L.Carenbauer,M.Seifert,K.W.Yang,“Structure/functionstudiesonmetal-β-lactamaseL1fromS.maltophilia”,J.Inorg.Biochem.1999,74,106.

K.W.Yang,Y.Z.Wang,Z.X.Huang*,J.Sun,“Activesitemodelofcarbonicanhydrase:synthesisandcrystalstructureoffunctionaltetrahedralzinccomplexwithhydrotris(3-phenyl-5-methylpyrazol-1-yl)borate”,Polyhedron,1997,16,109-112.

K.W.Yang,Y.Z.Wang,Z.X.Huang*,J.Sun,“Synthesis,characterizationandx-raycrystalstructureofZn(II)complexwithpoly-nitrogenligand[(3-HB(3,5-Me2pz)3]2Zn2C6H5CH3”,Polyhedron,1997,16,1297-1300.

YangK.W.,YinY.Q.,WangY.Z.,HuangZ.X.*,“Studiesonsynthesis,characterizationandquantumchemistryofcarbonicanhydraseactivesitemodelcompounds[(3-HB(3-Phpz)3ZnX](X=Cl,Br,IandNO3)”,ActaChimiaSinica,1997,55,209-214.

K.W.Yang,Y.Q.Yin,Z.X.Huang*,Y.H.Wang,“Synthesisandcrystalstructureofzinccomplex[Zn(P(py)3)2][Zn(NCS)4(MeCN)]”,Polyhedron,1996,15,79-81.

K.W.Yang,Y.Q.Yin*,D.S.Jin,“Anactivesitemodelforcarbonicanhydrase-synthesisandcrystalstructureof[(3-HB(3-Phpz)3]ZnBr”,Polyhedron,1995,14,1021-1023.

K.W.Yang,Y.Q.Yin*,D.S.Jin,“Preparationofcopper(I)complexeswithnovelpyrazolylborates”,Chi.Chem.Lett.1994,5,341-342.

YangK.W.,WuJ.G.,WangL.F.*,YangZ.Y.,“Determinationofstabilityconstantsofrareearth(III)complexesbyhypersensitivetransitionmethod”,J.LanzhouUni.(Nat.Sci),1994,30,49-52.

YangZ.Y.,WangL.F.*,WuJ.G.,YangK.W.,ZhuY.,“Studiesonsynthesis,characterizationandelectricalconductivityofcomplexesof3dtransitionmetalwith2-oxo-propionicacid(4-pyridinecarbonyl)hydrazone”,ActaChimiaSinica,1993,51,184-190.

YangK.W.,WuJ.G.,WangL.F.*,DongF.,“DeterminationofstabilityconstantsofNd(III)complexeswithpantothenatebyabsorptionspectroscopy”,Chi.J.Inorg.Chem.1993,9,271-274.

WangL.F.*,YangK.W.,WuJ.G.,“Determinationofthermodynamicalfunctionsofneodymiumpyridoxolcomplexesbyhypersensitivetransitionmethod”,Chi.J.Appl.Chem.1993,10,84-86.

YangZ.Y.,AiJ.,WangL.F.*,WuJ.G.,YangK.W.,“Studiesonthesynthesischaracterizationandantitumoractivityofthetemarycomplexesofrareearth(III)withschiffbase”,J.LanzhouUni.(Nat.Sci.),1993,29,162-166.

YangZ.Y.,WangL.F.*,WuJ.G.,LiX.Y.,YangK.W.,WangQ.,“Studiesonanticanceractivityofsomerareearth(III)complexeswithschifbase”,Chi.Sci.Bull.1992,9,813-816.

K.W.Yang,L.F.Wang*,J.G.Wu,F.Dong,“Synthesis,characterizationandantioxidativeactivityofnewvitaminB6triethanolaminerareearth(III)complexes”,J.Inorg.Biochem.1993,52,145-150.

K.W.Yang,L.F.Wang*,J.G.Wu,Z.Y.Yang,X.Gao,“Synthesis,characterizationandantioxidativeactivityofvitaminB6rareearth(III)complexes”,J.Inorg.Biochem.1993,52,151-155.


**MailingAddress:
Dr.KewuYang,CollegeofChemistryandMaterialsScience,NorthwestUniversity,229NorthTaibaiRd.Xi'an710069,PRChina.

Updated:March22,2014