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1、內皮抑素的多硫酸化肝素修飾及修飾物的二級結構和抗新生血管生成活性研究譚海寧?,?，王鳳山?*,?（?山東大學藥學院，?山東大學國家糖工程技術研究中心，山東濟南250012fax:0086-531-88382548;E-mail:fswang@sdu.edu.cn）CovalentModificationofEndostatinwithPolysulfatedHeparinandTheirSecondaryStructureandAnti-angiogenesisActivityStudyHainingTan?,?,YuhongLiu?,?andFengshanWang?*,?(I
2、nstituteofBiochemicalandBiotechnologicalDrug,SchoolofPharmaceuticalScience,ShandongUniversity,Jinan,250012,China,andNationalGlycoengineeringResearchCenter,ShandongUniversity,Jinan,250012,China.)ABSTRACTEndostatin(ES)isa20kDC-terminalfragmentofcollagenXVIIIthatinhibitsendothelialcellproliferat
3、ion,angiogenesisandthegrowthofseveralprimarytumors.However,someobstacleslimititsclinicaluse,suchasneedofhighdosetomaintainitsefficacy,expensive,andpoorstability,etc.Inordertoovercometheseshortcomings,wechemicallymodifiedESbypoly-sulfatedheparin(PSH).Westudiedtheinhibitionson131endothelialcell
4、proliferationandangiogenesisofESanditsmodifiedproduct,respectively.ThechangesofthesecondarystructurewerealsostudiedbyCirculardichroism(CD)spectratoobtainbetterESderivatives.OurstudydemonstratedthatthemodifiedproducthasabetterheattolerancethanESandtheinhibitionsonendothelialcellproliferationan
5、dangiogenesisisbetterthanES.Theresultofsecondary-structureanalysissuggestedthatthepercentageofβ-turninthemodifiedproduct,animportantfactorontheactivityandstability,hadlittlechangecomparedwiththatofES.Collectively,thesefindingsdemonstratedthatthemodifiedproductofES(PSH-ES),withlittlesecondarys
6、tructurechange,hasabetterheatstabilityandanti-angiogenesisactivitythanES.INTRODUCTIONNewbloodvesselsnourishingtumorgrowthformbyangiogenesis,whichmakeinhibitionofvesselformationanexcellenttargetforcancertherapy.Endostatin(ESAbbreviations:BCS,bovinecalfserum;CAM,chorioallantoicmembraneassay;CD,
7、Circulardichroism;CM-II,Carboxymethylcellulose-II;DS,degreeofsubstitution;ES,endostatin;HUVEC,humanumbilicalveinendothelialcell;IR,inhibitionratio;ISV,intersegmentalvessels;LMWH,lowmolecularweightheparin;MTT,3-(4,5-dimethylthiazol-2-yl)-2,5-d
