Binding investigation of integrin alphavbeta3 with its inhibitors by SPR technology and molecular docking simulation.

Integrins play critical roles in the process of angiogenesis and are attractive targets for anticancer therapies. It is desirable to develop new types of small-molecule inhibitors of integrin. Herein, the binding features of several inhibitors to integrin alpha(v)beta(3) have been studied by surface plasmon resonance (SPR) biosensor technology and molecular docking analyses. The SPR results indicated that the equilibrium dissociation constant (K(D)) values are evaluated for the inhibitors and showed that the K(D) value of cyclopeptide c-Lys is much lower than the reference molecule. In addition, the 3D structural model of integrin alpha(v)beta(3) was generated according to the crystal structure of the integrin alpha(v)beta(3) complex, and the molecular docking simulation analyses revealed that the predicted binding sites for the most active cyclopeptide c-Lys were consistent with the reported structure. These results thus implied that cyclopeptide c-Lys could be developed as a novel inhibitor for integrin alpha(v)beta(3). The current work has potential for application in structure-based integrin alpha(v)beta(3) inhibitor discovery.