Cancers, Vol. 9, Pages 128: Investigating the Interaction of Cyclic RGD Peptidomimetics with αVβ6 Integrin by Biochemical and Molecular Docking Studies

Cancers, Vol. 9, Pages 128: Investigating the Interaction of Cyclic RGD Peptidomimetics with αVβ6 Integrin by Biochemical and Molecular Docking Studies Cancers doi: 10.3390/cancers9100128 Authors: Monica Civera Daniela Arosio Francesca Bonato Leonardo Manzoni Luca Pignataro Simone Zanella Cesare Gennari Umberto Piarulli Laura Belvisi 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 p...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research