Overview:

Thrombomodulin(TM)isanintegralmembraneglycoproteinexpressedonthesurfaceofendothelialcells.ItsdiscoverybyEsmonandOwenhasfocusedattentionontheimportanceoftheproteinCanticoagulantpathway(1,2).TMservesasacofactorforproteinCactivationbyforminga1:1stoichiometriccomplexwiththrombin(Kd=10-10M),whichacceleratestherateofproteinCactivationby1000-foldrelativetotheratewiththrombinalone.InadditiontofacilitatingproteinCactivation,thebindingofthrombintoTMdrasticallyalterstheprocoagulantactivityofthrombin.WhenboundtoTM,thrombinnolongerclotsfibrinogen,activatesfactorV,inactivatesproteinSortriggersplateletaggregation.

TMisasinglechainproteincomposedof5distinctdomains.ThedomainstructureofTMissimilartothelowdensitylipoprotein(LDL)receptor.AshortcytoplasmicdomaincontainingafreecysteineislocatedattheCOOH-terminalendandisjoinedbyamembranespanningregiontoanO-glycosylationrichdomain.Thelatterisfollowedbyanepidermalgrowthfactor(EGF)homologyregionandtheNH2-terminalhydrophobicdomain.TheEGFhomologyregioncontains6EGF-likedomainsandcontainsthebindingsitesforboththrombinandproteinC.

Thrombomodulinisisolatedfromrabbitlungbyamodification(3)oftheproceduredescribedbyGalvinetal.(4)andissuppliedasanaqueoussolutionin0.02MTris,0.15MNaCl,pH7.4,containing0.05%polidocanol,andcanbestoredat-80°Cforuptoayear.PurityisdeterminedbySDS-PAGEanalysisandactivityisdeterminedusingachromogenicassayforproteinCactivation.

Properties:

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对生物制药的需求正在增长，并且该行业正在迅速采用外包策略，以作为满足不断升级的监管要求的一种方式。凭借在止血方面的丰富经验，HBS能够很好地协助开发影响凝血系统的药物产品。