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Biselectivity of isoDGR peptides for fibronectin binding integrin subtypes α5β1 and αvβ6: conformational control through flanking amino acids

Integrins are the major class of cell adhesion proteins. Their interaction with different ligands of the extracellular matrix is diverse. To get more insight into these interactions, artificial ligands endowed with a well-defined activity/selectivity profile are necessary. Herein, we present a libra...

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Main Authors: Bochen, Alexander (Author) , Marelli, Udaya Kiran (Author) , Otto, Elke (Author) , Pallarola, Diego (Author) , Mas-Moruno, Carlos (Author) , Di Leva, Francesco Saverio (Author) , Böhm, Heike (Author) , Spatz, Joachim P. (Author) , Novellino, Ettore (Author) , Kessler, Horst (Author) , Marinelli, Luciana (Author)
Format: Article (Journal)
Language:English
Published: January 30, 2013
In: Journal of medicinal chemistry
Year: 2013, Volume: 56, Issue: 4, Pages: 1509-1519
ISSN:1520-4804
DOI:10.1021/jm301221x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1021/jm301221x
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Author Notes:Alexander Bochen, Udaya Kiran Marelli, Elke Otto, Diego Pallarola, Carlos Mas-Moruno, Francesco Saverio Di Leva, Heike Boehm, Joachim P. Spatz, Ettore Novellino, Horst Kessler, and Luciana Marinelli
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Summary:Integrins are the major class of cell adhesion proteins. Their interaction with different ligands of the extracellular matrix is diverse. To get more insight into these interactions, artificial ligands endowed with a well-defined activity/selectivity profile are necessary. Herein, we present a library of cyclic pentapeptides, based on our previously reported peptide motif c(-phg-isoDGR-X-), in which high activity toward fibronectin binding integrins α5β1 and αvβ6 and not on vitronectin binding integrins αvβ3 and αvβ5 has been achieved by changing the flanking amino acids. The structure of the most promising candidates has been determined using a combined approach of NMR, distance geometry, and molecular dynamics simulations, and docking studies have been further used to elucidate the peptide-integrin interactions at the molecular level. The peptides’ binding affinity has been characterized by enzyme linked immunosorbent assay experiments, and the results have been verified by cell adhesion experiments on specifically functionalized surfaces.
Item Description:Gesehen am 27.11.2020
Physical Description:Online Resource
ISSN:1520-4804
DOI:10.1021/jm301221x

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