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Licensed Unlicensed Requires Authentication Published by De Gruyter June 1, 2005

Random Peptide Bacteriophage Display as a Probe for Urokinase Receptor Ligands

  • Susan Fong , Michael V. Doyle , Robert J. Goodson , Robert J. Drummond , Jennifer R. Stratton , Lisa McGuire , Laura V. Doyle , Harold A. Chapman and Steven Rosenberg
From the journal Biological Chemistry

Abstract

The urokinase receptor is a multifunctional protein that plays a central role in cell surface plasminogen activation, cell migration, and cell adhesion. We previously demonstrated that high affinity peptide ligands for the urokinase receptor, which are urokinase competitors, can be obtained from a 15mer peptide library (Goodson et al., 1994). In order to probe for additional urokinase receptor binding sites we affinity selected the same bacteriophage library on complexes of soluble urokinase receptor (suPAR) and the receptor binding domain of urokinase, residues 1 48 (uPA1 48). Bacteriophage were isolated which bound to suPAR and suPAR:uPA1 48 complexes with high yield. The peptide sequences encoded by these bacteriophage were distinct from those obtained previously on urokinase receptor expressing cells, and comprise two groups based upon effects on su PAR:1-anilino-8-napthalene sulfonate (ANS) fluorescence, and vitronectin binding competition. Alanine scanning mutagensis of the soluble peptides was used to define minimal regions and key residues for suPAR binding by competition with the parent bacteriophage. A comparison of these results with sequences of domains of both vitronectin and integrin αchains, which have been reported to be important for urokinase receptor binding, suggests that the homology with the peptide sequences selected is functionally significant.

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Published Online: 2005-06-01
Published in Print: 2002-01-23

Copyright © 2002 by Walter de Gruyter GmbH & Co. KG

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