| A peptide sequence from the EGF-2 like domain of FVII inhibits TF-dependent FX activation. | |
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MedLine Citation:
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PMID: 9172287 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have found that synthetic peptides derived from the two epidermal growth factor-like domains of factor VII are inhibitors of tissue factor dependent factor X activation. Inhibition was most pronounced for a constrained sequence of amino acids corresponding to positions 91-102 of factor VII, Cys-Val-Asn-Glu-Asn-Gly-Gly-Cys-Glu-Gin-Tyr-Cys. The biological activity appeared to be localized to the tripeptide 'motif', Glu-Gln-Tyr, within the larger sequence. The cyclic peptide was also an inhibitor of tissue factor induced coagulation of plasma, using lipidated tissue factor or tissue factor expressed on the surface of living cells. However, it did not interfere with intrinsic coagulation. Inhibition of factor X activation was dose-dependent with an IC50 value of 350 microM. Kinetic analyses revealed non-competitive inhibition with respect to factor X and suggested that the peptide sequence interferes with the factor VII/tissue factor/factor X complex formation and function. A pentapeptide analog of the putative pharmacophore was also a dose-dependent inhibitor of factor X activation with an IC50 value of 560 microM, but the tripeptide, Glu-Gin-Tyr, alone was without effect. Our results suggest a direct role for the second epidermal growth factor-like domain of factor VII, and in particular its loop I, in the formation and function of the factor VII/tissue factor/factor X complex. |
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Authors:
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L Orning; R W Stephens; L B Petersen; M J Hamers; H Stormorken; K S Sakariassen |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Thrombosis research Volume: 86 ISSN: 0049-3848 ISO Abbreviation: Thromb. Res. Publication Date: 1997 Apr |
Date Detail:
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Created Date: 1997-08-11 Completed Date: 1997-08-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0326377 Medline TA: Thromb Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 57-67 Citation Subset: IM |
Affiliation:
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Nycomed Imaging AS, Oslo, Norway. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Blood Coagulation / drug effects, physiology Epidermal Growth Factor / chemistry Factor VII / chemistry, genetics, physiology* Factor X / antagonists & inhibitors, physiology* Humans Kinetics Molecular Sequence Data Molecular Structure Peptide Fragments / chemistry, genetics, pharmacology* Thromboplastin / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Peptide Fragments; 62229-50-9/Epidermal Growth Factor; 9001-25-6/Factor VII; 9001-29-0/Factor X; 9035-58-9/Thromboplastin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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