Biselectivity of isoDGR peptides for fibronectin binding integrin subtypes α5β1 and αvβ6

• Verfasst von: Bochen, Alexander [VerfasserIn]
• Verfasst von: Marelli, Udaya Kiran [VerfasserIn]
• Verfasst von: Otto, Elke [VerfasserIn]
• Verfasst von: Pallarola, Diego [VerfasserIn]
• Verfasst von: Mas-Moruno, Carlos [VerfasserIn]
• Verfasst von: Di Leva, Francesco Saverio [VerfasserIn]
• Verfasst von: Böhm, Heike [VerfasserIn]
• Verfasst von: Spatz, Joachim P. [VerfasserIn]
• Verfasst von: Novellino, Ettore [VerfasserIn]
• Verfasst von: Kessler, Horst [VerfasserIn]
• Verfasst von: Marinelli, Luciana [VerfasserIn]
• Titel: Biselectivity of isoDGR peptides for fibronectin binding integrin subtypes α5β1 and αvβ6
• Titelzusatz: conformational control through flanking amino acids
• Verf.angabe: 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
• E-Jahr: 2013
• Jahr: January 30, 2013
• Umfang: 11 S.
• Fussnoten: Gesehen am 27.11.2020
• Titel Quelle: Enthalten in: Journal of medicinal chemistry
• Ort Quelle: Washington, DC : ACS, 1959
• Jahr Quelle: 2013
• Band/Heft Quelle: 56(2013), 4, Seite 1509-1519
• ISSN Quelle: 1520-4804
• DOI: doi:10.1021/jm301221x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1741386519

Abstract

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.