Design and synthesis of pH-responsive polymers with dipeptide side-chain pendants for supramolecular self-assembly

Peptide-containing polymers have attracted significant interest owing to their biocompatibility and capability to form well-defined supramolecular assemblies through noncovalent interactions. In this work, a series of phenylalanine-based dipeptide methacrylate monomers with varied stereochemical configurations was synthesized and further polymerized using the reversible addition-fragmentation chain transfer (RAFT) method to obtain well-defined dipeptide side-chain polymers, P(Boc-dipeptide-EMA), exhibiting controlled molecular weights, narrow dispersity (Ð), and well-defined chain-end functionality. In addition, the monomers were polymerized via RAFT polymerization using a monomethoxy poly(ethylene glycol) (mPEG) based macro chain transfer agent, leading to the formation of amphiphilic block copolymers, mPEG-b-P(Boc-dipeptide-EMA). Following Boc-deprotection, the resulting homo- and block copolymers exhibited pH-responsive properties and contained pendant primary amine groups. The critical aggregation concentration (CAC) of the block copolymers in aqueous solution was determined by pyrene fluorescence spectroscopy. Dynamic light scattering (DLS) and atomic force microscopy (AFM) further confirmed the formation of nanoscale aggregates. The combination of pH-responsive behavior and peptide pendants makes these polymers attractive building blocks for the design of functional nanostructured materials with potential biomedical applications.