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《（新編）內(nèi)皮抑素的多硫酸化肝素修飾及修飾物的二級(jí)結(jié)構(gòu)和抗新生血管生成活性研究》由會(huì)員上傳分享，免費(fèi)在線閱讀，更多相關(guān)內(nèi)容在教育資源-天天文庫。
1、內(nèi)皮抑素的多硫酸化肝素修飾及修飾物的二級(jí)結(jié)構(gòu)和抗新生血管生成活性研究譚海寧?,?，王鳳山?*,?（?山東大學(xué)藥學(xué)院，?山東大學(xué)國家糖工程技術(shù)研究中心，山東濟(jì)南250012fax:0086-531-88382548;E-mail:fswang@sdu.edu.cn）CovalentModificationofEndostatinwithPolysulfatedHeparinandTheirSecondaryStructureandAnti-angiogenesisActivityStudyHainingTan?,?,YuhongL
2、iu?,?andFengshanWang?*,?(InstituteofBiochemicalandBiotechnologicalDrug,SchoolofPharmaceuticalScience,ShandongUniversity,Jinan,250012,China,andNationalGlycoengineeringResearchCenter,ShandongUniversity,Jinan,250012,China.)ABSTRACTEndostatin(ES)isa20kDC-terminalfragment
3、ofcollagenXVIIIthatinhibitsendothelialcellproliferation,angiogenesisandthegrowthofseveralprimarytumors.However,someobstacleslimititsclinicaluse,suchasneedofhighdosetomaintainitsefficacy,expensive,andpoorstability,etc.Inordertoovercometheseshortcomings,wechemicallymod
4、ifiedESbypoly-sulfatedheparin(PSH).Westudiedtheinhibitionson24endothelialcellproliferationandangiogenesisofESanditsmodifiedproduct,respectively.ThechangesofthesecondarystructurewerealsostudiedbyCirculardichroism(CD)spectratoobtainbetterESderivatives.Ourstudydemonstra
5、tedthatthemodifiedproducthasabetterheattolerancethanESandtheinhibitionsonendothelialcellproliferationandangiogenesisisbetterthanES.Theresultofsecondary-structureanalysissuggestedthatthepercentageofβ-turninthemodifiedproduct,animportantfactorontheactivityandstability,
6、hadlittlechangecomparedwiththatofES.Collectively,thesefindingsdemonstratedthatthemodifiedproductofES(PSH-ES),withlittlesecondarystructurechange,hasabetterheatstabilityandanti-angiogenesisactivitythanES.INTRODUCTIONNewbloodvesselsnourishingtumorgrowthformbyangiogenesi
7、s,whichmakeinhibitionofvesselformationanexcellenttargetforcancertherapy.Endostatin(ESAbbreviations:BCS,bovinecalfserum;CAM,chorioallantoicmembraneassay;CD,Circulardichroism;CM-II,Carboxymethylcellulose-II;DS,degreeofsubstitution;ES,endostatin;HUVEC,humanumbilicalvein
8、endothelialcell;IR,inhibitionratio;ISV,intersegmentalvessels;LMWH,lowmolecularweightheparin;MTT,3-(4,5-dimethylthiazol-2-yl)-2,5-di
