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A synthetic peptide derived from staphylokinase enhances plasminogen activation by tissue-type plasminogen activator.
- Source :
-
Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2011 May; Vol. 9 (5), pp. 997-1006. - Publication Year :
- 2011
-
Abstract
- Background: A synthetic nonadecapeptide (SP; GPYLMVNVTGVDGKGNELL) previously enhanced the activation of plasminogen by the SAK/plasmin complex.<br />Objectives: To identify the binding site for SP on plasminogen and elucidate the effects of SP on plasminogen activation by the tissue-type plasminogen activator (t-PA).<br />Methods: The effects of SP on plasminogen activation were estimated using a chromogenic substrate and from the cleavage of plasmin on SDS-PAGE under reduced conditions. The binding to SP of various peptides derived from the amino acid sequence of plasminogen was analyzed with an IAsys biosensor. The SP-mediated structural change to plasminogen was analyzed by circular dichroism (CD) spectroscopy. The thrombolytic effects of SP were examined using a mouse model of thrombosis.<br />Results: SP enhanced the activation of plasminogen by t-PA. The catalytic efficiency (k(cat)/K(m)) of Glu-plasminogen activation by t-PA was 11.4-fold higher in the presence than absence of SP. The binding of SP to plasminogen was greatly inhibited by a synthetic peptide, FEKDKYILQGVTSWGLG, located close to the C-terminal of the plasminogen B region. Near-ultraviolet CD spectra of the complex between SP and Glu-plasminogen significantly differed from those of Glu-plasminogen. When SP was administered in a mouse model of thrombosis, early recanalization was observed in a dose-dependent manner. However, SP did not cause recanalization in t-PA gene-deficient mice.<br />Conclusions: SP bound to the B region and promoted the activation of plasminogen by t-PA, and then induced effective thrombolysis.<br /> (© 2011 International Society on Thrombosis and Haemostasis.)
- Subjects :
- Amino Acid Sequence
Animals
Binding Sites
Circular Dichroism
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Endothelial Cells metabolism
Humans
Kinetics
Mice
Molecular Sequence Data
Protein Binding
Thrombolytic Therapy
Thrombosis metabolism
Metalloendopeptidases chemistry
Peptides chemistry
Plasminogen chemistry
Tissue Plasminogen Activator metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7836
- Volume :
- 9
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and haemostasis : JTH
- Publication Type :
- Academic Journal
- Accession number :
- 21392255
- Full Text :
- https://doi.org/10.1111/j.1538-7836.2011.04257.x