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Cancers 2017, 9(10), 128;

Investigating the Interaction of Cyclic RGD Peptidomimetics with αVβ6 Integrin by Biochemical and Molecular Docking Studies

Dipartimento di Chimica, Università degli Studi di Milano, via Golgi 19, I-20133 Milano, Italy
Istituto di Scienze e Tecnologie Molecolari (I.S.T.M.), Consiglio Nazionale delle Ricerche (C.N.R.), via Golgi 19, I-20133 Milano, Italy
Dipartimento di Scienza e Alta Tecnologia, Università degli Studi dell’Insubria, via Valleggio 11, I-22100 Como, Italy
Author to whom correspondence should be addressed.
Academic Editor: Helen M. Sheldrake
Received: 11 August 2017 / Revised: 13 September 2017 / Accepted: 18 September 2017 / Published: 21 September 2017
(This article belongs to the Special Issue Integrins in Cancer)
PDF [1356 KB, uploaded 21 September 2017]


The interaction of a small library of cyclic RGD (Arg-Gly-Asp) peptidomimetics with αVβ6 integrin has been investigated by means of competitive solid phase binding assays to the isolated receptor and docking calculations in the crystal structure of the αVβ6 binding site. To this aim, a rigid receptor-flexible ligand docking protocol has been set up and then applied to predict the binding mode of the cyclic RGD peptidomimetics to αVβ6 integrin. Although the RGD interaction with αVβ6 recapitulates the RGD binding mode observed in αVβ3, differences between the integrin binding pockets can strongly affect the ligand binding ability. In general, the peptidomimetics exhibited IC50 values for integrin αVβ6 (i.e., the concentration of compound required for 50% inhibition of biotinylated fibronectin binding to isolated αVβ6 integrin) in the nanomolar range (77–345 nM), about 10–100 times higher than those for the related αVβ3 receptor, with a single notable ligand displaying a low nanomolar IC50 value (2.3 nM). Insights from the properties of the binding pocket combined with the analysis of the docking poses provided a rationale for ligand recognition and selectivity. View Full-Text
Keywords: RGD peptidomimetics; integrins; molecular docking; binding assays RGD peptidomimetics; integrins; molecular docking; binding assays

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Civera, M.; Arosio, D.; Bonato, F.; Manzoni, L.; Pignataro, L.; Zanella, S.; Gennari, C.; Piarulli, U.; Belvisi, L. Investigating the Interaction of Cyclic RGD Peptidomimetics with αVβ6 Integrin by Biochemical and Molecular Docking Studies. Cancers 2017, 9, 128.

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