Novel Linear Peptides with High Affinity to αvβ3 Integrin for Precise Tumor Identification

Development of alternative linear peptides for targeting alpha v beta 3 integrin has attracted much attention, as the traditional peptide ligand, cyclic RGD, is limited by inferior water-solubility and complex synthesis. Using pharmacophore-based virtual screening and high-throughput molecular docking, we identified two novel linear small peptides RWr and RWrNM with high affinity and specificity to alpha v beta 3 integrin. The competitive binding with cyclic RGD (c(RGDyK)) and cellular uptake related to the integrin expression levels verified their affinity to alpha v beta 3 integrin. The intermolecular interaction measurement and dynamics simulation demonstrated the high binding affinity and stability, especially for RWrNM. In vivo peptide-guided tumor imaging and targeted therapy further confirmed their specificity. Results indicated that the newly identified small linear peptide RWrNM, with high affinity and specificity to alpha v beta 3 integrin, better water-solubility, and simplified synthetic process, could overcome limitations of the current cyclic RGD peptides, paving the way for diverse use in diagnosis and therapy.