Modeling the Interaction of Low Molecular Weight Targeting Ligands and Synthesis of Lipotripeptides with Potential Inhibitory Ability Against Integrin αVβ3

Low molecular weight RGD peptides and RGD mimetics are widely studied as ligands targeting the corresponding receptor in the diagnosis and therapy of cancer, as well as in the field of bone tissue regeneration. Some of them are undergoing preclinical trials. The aim of this study is to select the optimal variants of the ligand structure based on an aliphatic RGD mimetic. By methods of molecular modeling (blind docking and active site docking), the most advantageous constructions for the formation of a stable complex with the integrin α_Vβ₃ are determined. A scheme is developed and two lipotripeptides Gnd-GABA-Gly-Asp(C₁₆)₂ and Gnd-β-Ala-Gly-Asp(C₁₆)₂ with the potential ability to inhibit this receptor on the surface of tumor tissues are synthesized.