Molecular basis for the targeted binding of RGD-containing peptide to integrin αVβ3

Integrin alpha(V)beta(3)-targeting peptides with an exposedarginine-glycine-aspartate (RGD) sequence play a crucial role in targeted anticancer drug delivery. The effects of RGD-containing peptide structure and quantity on mechanism of targeted binding of RGD-containing peptide to integrin alpha(V)beta(3) were studied intensively at the molecular level via molecular dynamic simulations. Targeted recognization was mainly driven by the electrostatic interactions between the residues in RGD and the metal ions in integrin alpha(V)beta(3), and cyclic arginine-glycine-aspartate phenylalanine valine (RGDFV) peptide appeared to be a better vector than the linear RGD-containing peptides. In addition, the optimal molar concentration ratio of RGD peptides to integrin alpha(V)beta(3) appeared to be 2:1. These results will help improve the current understanding on the mechanism of interactions between RGD and integrin alpha(V)beta(3), and promote the application prospects of RGD-based vectors in tumor imaging, diagnosis, and cancer therapy. (C) 2013 Elsevier Ltd. All rights reserved.