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A Synthetic Peptide Derived From Staphylokinase Enhances Plasminogen Activation by Tissue-Type Plasminogen Activator

A Synthetic Peptide Derived From Staphylokinase Enhances Plasminogen Activation by Tissue-Type Plasminogen Activator

K Okada, S Ueshima, H Matsuno, N Nagai, N Kawao, M Tanaka, O Matsuo

J Thromb Haemost. 2011 May;9(5):997-1006.

PMID: 21392255

Abstract:

Background:
A synthetic nonadecapeptide (SP; GPYLMVNVTGVDGKGNELL) previously enhanced the activation of plasminogen by the SAK/plasmin complex.
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).
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.
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.
Conclusions:
SP bound to the B region and promoted the activation of plasminogen by t-PA, and then induced effective thrombolysis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4246520	Tissue plasminogen activator chromogenic substrate			Price

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