Green Synthesis of a Hyaluronan-Based Multimeric A9 Peptide System: Polysaccharide-A9 Conjugate with Enhanced HER2 Receptor Binding Affinity and Potential Biomedical Applications as an Active Material

A solid-state strategy for conjugating the peptide sequence A9 to hyaluronic acid (HA) has been developed via mechanosynthesis promoted by microwave radiation. The method employs a silica-supported nucleophilic catalyst (DMAP) to activate the carboxylic groups of the polysaccharide, enabling efficient conjugation. These conditions minimize waste generation, enhancing environmental sustainability and operator safety while ensuring a high yield of the final HA-A9 conjugate. The multicopy HA-A9 system exhibits enhanced affinity toward a synthetic HER2 receptor model. Furthermore, the HA-A9 conjugate demonstrates the ability to self-assemble into micellar aggregates and form viscous materials enriched with β-sheet peptide structures. These supramolecular assemblies highlight the potential of conjugates for biomedical applications.