Polymer Nanoparticles with Uniform Monomer Sequences for Sequence‐Specific Peptide Recognition

Synthetic polymer nanoparticles (NPs) that recognize and neutralize target biomacromolecules are of considerable interest as “plastic antibodies”, synthetic mimics of antibodies. However, monomer sequences in the synthetic NPs are heterogeneous. The heterogeneity limits the target specificity and safety of the NPs. Herein, we report the synthesis of NPs with uniform monomer sequences for recognition and neutralization of target peptides. A multifunctional oligomer with a precise monomer sequence that recognizes the target peptide was prepared via cycles of reversible addition–fragmentation chain transfer (RAFT) polymerization and flash chromatography. The oligomer or blend of oligomers was used as a chain transfer agent and introduced into poly(N‐isopropyl acrylamide) hydrogel NPs by radical polymerization. Evaluation of the interaction with the peptides revealed that multiple oligomers in NPs cooperatively recognized the sequence of the target peptide and neutralized its toxicity. Effect of sequence, combination, density and molecular weight distribution of precision oligomers on the affinity to the peptides was also investigated. Polymer nanoparticles with uniform monomer sequences for target recognition were synthesized for the first time by polymerizing nanoparticles in the presence of sequence‐precise oligomers. The oligomers cooperatively recognized the amino acid sequence of the target peptide and neutralized its toxicity. This is the first step towards achieving a “monoclonal plastic antibody”, a synthetic polymer with a uniform monomer sequence for target‐specific neutralization.