Homogeneous Oligomeric Ligands Prepared via Radical Polymerization that Recognize and Neutralize a Target Peptide

• Published in: Angewandte Chemie International Edition Vol. 59; no. 2; pp. 679 - 683
• Main Authors: Hoshino, Yu, Taniguchi, Shohei, Takimoto, Hinata, Akashi, Sotaro, Katakami, Sho, Yonamine, Yusuke, Miura, Yoshiko
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 07.01.2020
• Edition: International ed. in English
• Subjects: Antibodies; Aptamers; Biomolecules; block copolymers; combinatorial chemistry; Epitopes; Functional groups; homogeneous oligomer; Humans; Ligands; Monomers; Oligomers; Peptides; Peptides - chemistry; Polymerization; synthetic ligand; Target recognition; Toxicity; block copolymers; polymerization; combinatorial chemistry; homogeneous oligomer; synthetic ligand
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201910558

Abiotic ligands that bind to specific biomolecules have attracted attention as substitutes for biomolecular ligands, such as antibodies and aptamers. Radical polymerization enables the production of robust polymeric ligands from inexpensive functional monomers. However, little has been reported about the production of monodispersed polymeric ligands. Herein, we present homogeneous ligands prepared via radical polymerization that recognize epitope sequences on a target peptide and neutralize the toxicity of the peptide. Taking advantage of controlled radical polymerization and separation, a library of multifunctional oligomers with discrete numbers of functional groups was prepared. Affinity screening revealed that the sequence specificity of the oligomer ligands strongly depended on the number of functional groups. The process reported here will become a general step for the development of abiotic ligands that recognize specific peptide sequences. Homogeneous oligomeric ligands that recognize epitope sequences on a target peptide and neutralize its toxicity have been prepared via radical polymerization of commercial bulk materials. These synthetic ligands, prepared by controlled radical polymerization, oligomer separation, and affinity screening, are an attractive alternative to biomolecular ligands.