水蛭素的分子改造与结构修饰研究进展-王航

王航,许静,谭树华*(,210009):为更好地开发利用重组水蛭素,综述国内外水蛭素结构修饰研究状况依据近年来国内外文献,进行分析归纳和总结笔者通过对水蛭素进行各种分子改造或者结构修饰来产生新的类似物蛋白,从而解决水蛭素在临床应用中出现的种种问题,有的也可能会出现新的功能:水蛭素;不良反应;结构修饰doi:10.3969/j.issn.1004-2407.2011.05.032:R914:A:1004-2407(2011)05-0385-03AdvancesinthestudyofstructuralmodificationsofhirudinWANGHang,XUJing,TANShuhua*(MolecularBiologyDepartment,SchoolofLifeScience&Technology,ChinaPharmaceut-icalUniversity,JiangsuNanjing210009,China)Abstract:ObjectiveTostudythestructuralmodificationsofhirudin.MethodsBasedonliteratures,theresearchprogressinhirudinstructuralanalogueswasanalyzedandsummarized.ResultandConclusionHirudinhasbeenmodifiedwithmoleculartransforma-tionandstructuralmodifications.Theobtainedproteinscanalleviateadversereactioninclinical,orbringnewfunctions,suchasthrombolysis,inhibitingtheplateletaggregation,andtargetingspecifically.Keywords:hirudin;adversereactions;structuralmodifications:(:30873191):,,*:,,1986,,[1],;,,,1,,;,,,,,,,;,,,[2],[3],5d74%(AHAb)2003,Greinacher94,2,,,,,2.1水蛭素融合蛋白,,,,[4]2.1.1-,,,,1XaLian[5]11Y,N,,2.1.2-,[6]FXaN,NFXa,,FXFXa,,,,2.2RGD-重组双功能水蛭素RGD--,385201110265[7]1984RGD,RGDRGDGPÒb/Óa,RGD,,RGDGPIlb/Óa,,,RGD[8],RGDGPÒb/Óa,[9]RGD,,,2,1/2~1/3,,,[10]2.3多功能融合水蛭素2005,SzemrajCRGD,,,,Szemraj[11],Kowalski[12]:,2.4聚乙二醇修饰水蛭素(PEG)2070,,,;,[13],,Ò,[14-15]3,:,,,,Cen[16],-,,,,[17],Ó,EDTA-2Na,Ó,,,,[18],D-,,D-,(SOD),(MDA),,,,420,,21FDAAngiamax20,HITHIT,,,,,,,,,:[1],菂.水蛭素与凝血酶作用的探讨[J].西北药,2007,22(2):95-96.[2]AndreasG,TheodoreEW.Thedirectthrombininhib-itor-hirudin[J].Thrombinhaemost,2008,99:819-829.[3].[J].,2007,16(3):181-187.[4],,,.[J].,2007,15(1):215-218.[5]LianQ,SzarkaSJ,NgKK,etal.Engineeringofastaphy-lokinase-basedfibrinolyticagentwithantithromboticac-tivityandtargetingcapabilitytowardthrombin-richf-ibrinandplasmaclots[J].BiolChem,2003,278:26677-26686.[6],,,.[J].,2006,26(4):36-39.[7],,.RGD[J].,2010,31(1):66-69.[8],,,.RGD[J].,2010,31(2):209-212.[9]PeneS.Tirofibantherapytipsthescalesafterangioplas-ty[J].InpharmaWeekly,2008,1655:11-12.[10],,,.[J].,2006,2(22):106-108.[11]SzemrajJ,StankiewiczA,Rozmyslowicz-SzermiskaW,386201110265[J].ThrombHaemost,2007,97(6):1037-1045.[12]KowalskiM,BrownG,BieniaszM,etal.Cloningandex-pressionofanewrecombinantthrombolyticandan-thithromboticagentastaphylokinasevariant[J].ActaBiochimPol,2009,56(1):41-53.[13],,,.[J].:,2007,15(4):586-590.[14]HeiseM,SchmidmaierG,HusmannI,etal.PEG-hiru-din/iloprostcoatingofsmalldiameterePTFEgraftsef-fectivelypreventspseudointimaandintimalhyperplasiadevelopment[J].EurJVascEndovascSurg,2006,32(4):418-424.[15]UlbrichtK,BuchaE,PoschelKA,etal.TheuseofPEG-HirudininchronichemodialysismonitoredbytheEcarinClottingTime:influenceonclottingoftheextracorporealsystemandhemostaticparameters[J].ClinNephrol,2006,65(3):180-190.[16]CenXD,NiJQ,TanTC,etal.Investigationonrecomb-inanthirudinviaoralroute[J].Peptides,2006,27(4):836-840.[17],,,.Ó[J].,2007,42(3):197-200.[18],,,.[J].,2005,36(3):260-262.(:2011-04-01)PK-PD李冉,金青*(,266042):对心血管系统药物的药动学-药效学(PK-PD)模型研究进行回顾和展望查阅文献资料,对相关内容进行总结所得PK-PD模型以S-Emax模型居多心血管系统药物的PK-PD模型日益呈现出精细化和复杂化的趋势应用PK-PD模型对心血管系统药物的研究前景广阔,值得进一步推广:心血管药物;药动学;药效学;模型doi:10.3969/j.issn.1004-2407.2011.05.033:R94:A:1004-2407(2011)05-0387-03:,,*:,,,2008,299,,,(pharmacokinetics,PK)(phar-macodynamics,PD),PK-PD,,(),[1-2]PK-PD1PK-PDPK-PD44[3]:1.1直接连接模型和间接连接模型,,,PK-PD,,PDSEmaxVanSteeg[4]S(-)-(WKY),,PDS-EmaxPK/PDB,,ADAPTII[5],PK-PDSEmax1.2直接反应模型和间接反应模型,PK-PD,,,,,PK-PD:HaoK.[6],2,PK-PD,,1.3软连接模型与硬连接模型387201110265