Solvent-Free procedure of an A9 Peptide Dimer Exhibiting Specific HER2 Receptor Binding: Fluorescence Spectroscopy Evaluation of the Enhanced Binding Affinity

HER2-expressing cancers currently benefit from targeted therapies, including monoclonal antibodies and antibody-drug conjugates that specifically bind to the extracellular domain of the receptor. Peptides targeting HER2 represent promising candidates for the development of alternative molecular drugs. In this study, we report a dimeric version of the previously validated A9 peptide as a ligand specifically targeting HER2. The novel A9-PEG-A9 conjugate consists of two A9 peptides whose N-terminal amino groups are linked via a polyethylene glycol chain. It was synthesized using a solvent-free protocol and validated as an improved ligand, demonstrating enhanced water solubility and increased affinity for the model receptor HER2-DIVMP, as determined by the fluorescence spectroscopy titration method.