Biselectivity of isoDGR peptides for fibronectin binding integrin subtypes alpha5beta1 and alphavbeta6: conformational control through flanking amino acids.

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Bochen A, Marelli UK, Otto E, Pallarola D, Mas-Moruno C, Di Leva FS, Boehm H, Spatz JP, Novellino E, Kessler H, Marinelli L

Biselectivity of isoDGR peptides for fibronectin binding integrin subtypes alpha5beta1 and alphavbeta6: conformational control through flanking amino acids.

J Med Chem. 2013 Feb 28;56(4):1509-19. doi: 10.1021/jm301221x. Epub 2013 Feb 18.

PubMed ID
23362923 [ View in PubMed
]
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 alpha5beta1 and alphavbeta6 and not on vitronectin binding integrins alphavbeta3 and alphavbeta5 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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
TirofibanIntegrin beta-3IC 50 (nM)0.95N/AN/ADetails