Inhibition of the interaction of urokinase-type plasminogen activator (uPA) with its receptor (uPAR) by synthetic peptides
| Autor: | Bernhard König, Henner Graeff, Lothar Goretzki, Marcus Koppitz, Olaf Wilhelm, Josef Kellermann, Horst Kessler, Ulrich H. Weidle, Christoph Riemer, Ute Reuning, Markus Bürgle, Friedrich Lottspeich, Viktor Magdolen, Manfred Schmitt |
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| Rok vydání: | 1997 |
| Předmět: |
Clinical Biochemistry
Molecular Sequence Data Peptide Receptors Cell Surface Ligands Biochemistry Mass Spectrometry Receptors Urokinase Plasminogen Activator Tumor Cells Cultured Humans Amino Acid Sequence skin and connective tissue diseases neoplasms Molecular Biology Peptide sequence Chromatography High Pressure Liquid chemistry.chemical_classification Serine protease biology Flow Cytometry Molecular biology Urokinase-Type Plasminogen Activator biological factors Cyclic peptide Amino acid Urokinase receptor chemistry biology.protein Vitronectin Peptides Plasminogen activator |
| Zdroj: | Biological chemistry. 378(3-4) |
| ISSN: | 1431-6730 |
| Popis: | Focusing of the serine protease urokinase-type plasminogen activator (uPA) to the cell surface via interaction with its specific receptor (uPAR, CD87) is an important step for tumor cell invasion and metastasis. The ability of a synthetic peptide derived from the uPAR-binding region of uPA (comprising amino acids 16-32 of uPA; uPA(16-32)) to inhibit binding of fluorescently labeled uPA to uPAR on human promyeloid U937 cells was assessed by quantitative flow cytofluorometric analysis (FACS) and compared to the inhibitory capacities of other synthetic peptides known to interfere with uPA/uPAR-interaction. An about 3000-fold molar excess of uPA(16-32) resulted in 50% inhibition of pro-uPA binding to cell surface-associated uPAR. Using a solid-phase uPA-ligand binding assay employing recombinant soluble uPAR coated to microtiter plates, the minimal binding region of wild-type uPA was determined. The linear peptide uPA(19-31) and its more stable disulfide-bridged cyclic form (cyclo(19,31)uPA(19-31)) displayed uPAR-binding activity whereas other peptides such as uPA(18-30), uPA(20-32) or uPA(20-30) did not react with uPAR. Cyclic peptide derivatives of cyclo(19,31)uPA(19-31) in which certain amino acids were deleted and/or replaced by other amino acids as well as uPAR-derived wild-type peptides did also not inhibit uPA/uPAR-interaction. Therefore, the present investigations identified cyclo(19,31)uPA(19-31) as a potential lead structure for the development of uPA-peptide analogues to block uPA/uPAR-interaction. |
| Databáze: | OpenAIRE |
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