title: Molecular basis for the targeted binding of RGD-containing peptide to integrin αVβ3.
abstract: Integrin αVβ3-targeting peptides with an exposed arginine-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 αVβ3 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 αVβ3, 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 αVβ3 appeared to be 2:1. These results will help improve the current understanding on the mechanism of interactions between RGD and integrin αVβ3, and promote the application prospects of RGD-based vectors in tumor imaging, diagnosis, and cancer therapy.
authors.affiliation: Soft Matter Research Center, Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Yu
authors.affiliation: Soft Matter Research Center, Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Soft Matter Research Center, Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China. Electronic address: liuyingch@zju.edu.cn.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, Peking University, Beijing 100191, PR China. Electronic address: bmuxieying@bjmu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
mesh_terms: D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008958:Models, Molecular; D009842:Oligopeptides / Q000378:metabolism*; D011485:Protein Binding; D055672:Static Electricity
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid
keywords: Integrin α(V)β(3); Interaction mechanism; Molecular dynamic simulation; RGD; Targeted binding