Insights into the Binding of Cyclic RGD Peptidomimetics to a5b1 Integrin by using Live-Cell NMR And Computational Studies
Articolo
Data di Pubblicazione:
2017
Citazione:
Insights into the Binding of Cyclic RGD Peptidomimetics to a5b1 Integrin by using Live-Cell NMR And Computational Studies / I. Guzzetti, M. Civera, F. Vasile, D. Arosio, C. Tringali, U. Piarulli, C. Gennari, L. Pignataro, L. Belvisi, D. Potenza. - In: CHEMISTRYOPEN. - ISSN 2191-1363. - 6:1(2017 Feb), pp. 128-136. [10.1002/open.201600112]
Abstract:
The interaction of a small library of cyclic DKP–RGD peptidomimetics with α5β1 integrin has been investigated by means of an integrated experimental and computational approach. Bioaffinity NMR techniques, including saturation transfer difference (STD) and transferred NOESY, were applied to the ligands in a suspension of intact MDA-MB-231 breast cancer cells, in which integrin α5β1 is highly expressed. The NMR data were compared with the docking calculations of the RGD ligands in the crystal structure of the α5β1 binding site, and were integrated with competitive binding assays to the purified α5β1 integrin. Ligand binding epitopes involve protons of both the RGD moiety and the DKP scaffold, although the stereochemistry and the functionalization of the DKP scaffold as well as the macrocycle conformation determine a great variability in the interaction. The ligand showing the highest number of STD signals is also the most potent α5β1 ligand of the series, displaying a nanomolar IC50 value.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
integrins; ligand-protein interactions; molecular docking; RGD peptidomimetics; NMR spectroscopy
Elenco autori:
I. Guzzetti, M. Civera, F. Vasile, D. Arosio, C. Tringali, U. Piarulli, C. Gennari, L. Pignataro, L. Belvisi, D. Potenza
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