Related Experiment Video
Updated: Jun 12, 2026

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Investigating the Interaction of Cyclic RGD Peptidomimetics with αVβ₆ Integrin by Biochemical and Molecular Docking
Monica Civera1,2, Daniela Arosio3, Francesca Bonato4
1Dipartimento di Chimica, Università degli Studi di Milano, via Golgi 19, I-20133 Milano, Italy. monica.civera@unimi.it.
Abstract:
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.
Related Concept Videos
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-protein Interfaces
Integrins
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Intracellular Signaling Affects Focal Adhesions
Some...

