Dynamic Anchoring of Peptides to the Extracellular Matrix Enabled by Boronic Acid

Given the extracellular matrix (ECM) essential role in tissue development, maintenance, and repair, exploiting its glycan structures offers new opportunities for dynamic drug storage and targeted delivery of peptides via injectable solutions. This study investigates the reversible, pH-driven interaction between boronic acid-functionalized compounds and diol-rich glycans within cell-derived decellularized extracellular matrices (CDMs). An N-terminally functionalized model peptide was produced using carboxy-phenyl-boronic acid (CPBA), and its pH-dependent binding to the diol-rich structures of CDMs was demonstrated. A CPBA-conjugated myostatin inhibitor maintained its full potency as a prerequisite for future therapeutic application. The findings suggest N-terminally boronic acid-modified peptides as drug candidates for targeted delivery and storage to diol-rich glycans of the natural ECM.