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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2008-2-11
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pubmed:abstractText |
A recombinant prodrug, single-chain urokinase-type plasminogen activator (scuPA) fused to an anti-PECAM-1 antibody single-chain variable fragment (anti-PECAM scFv/scuPA) targets endothelium and augments thrombolysis in the pulmonary vasculature.(1) To avoid premature activation and inactivation and to limit systemic toxicity, we replaced the native plasmin activation site in scFv/low-molecular-weight (lmw)-scuPA with a thrombin activation site, generating anti-PECAM scFv/uPA-T that (1) is latent and activated by thrombin instead of plasmin; (2) binds to PECAM-1; (3) does not consume plasma fibrinogen; (4) accumulates in mouse lungs after intravenous injection; and (5) resists PA inhibitor PAI-1 until activated by thrombin. In mouse models of pulmonary thrombosis caused by thromboplastin and ischemia-reperfusion (I/R), scFv/uPA-T provided more potent thromboprophylaxis and greater lung protection than plasmin-sensitive scFv/uPA. Endothelium-targeted thromboprophylaxis triggered by a prothrombotic enzyme illustrates a novel approach to time- and site-specific regulation of proteolytic reactions that can be modulated for therapeutic benefit.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-10051650,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-10332019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-10368124,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-10806208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-11156884,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-11329062,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-11493451,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-11521996,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-11861781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-12244306,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-12461559,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-12531816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-12629066,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-12652312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-14500967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-15099287,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-16144802,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-16296786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-17389242,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-1918077,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-1946453,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-2953770,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-3081506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-3116546,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-7544349,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-7586274,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-7671373,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-8286392,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-8550840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-8930213,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-9024162,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-9120018,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-9413397,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18045968-9923894
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
111
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1999-2006
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18045968-Humans,
pubmed-meshheading:18045968-Animals,
pubmed-meshheading:18045968-Mice,
pubmed-meshheading:18045968-Thrombin,
pubmed-meshheading:18045968-Fibrinogen,
pubmed-meshheading:18045968-Male,
pubmed-meshheading:18045968-Pulmonary Circulation,
pubmed-meshheading:18045968-Endothelium, Vascular,
pubmed-meshheading:18045968-Protein Binding,
pubmed-meshheading:18045968-Tissue Distribution,
pubmed-meshheading:18045968-Urokinase-Type Plasminogen Activator,
pubmed-meshheading:18045968-Mice, Inbred C57BL,
pubmed-meshheading:18045968-Thrombolytic Therapy,
pubmed-meshheading:18045968-Recombinant Proteins,
pubmed-meshheading:18045968-Recombinant Fusion Proteins
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