On-Resin Recognition of Aromatic Oligopeptides and Proteins through Host-Enhanced Heterodimerization

Abstract

Peptide dimerization is ubiquitous in natural protein conjugates and artificial self-assemblies. A major challenge in artificial systems remains achieving quantitative heterodimerization of peptides, critical for next-generation biomolecular purification and formulation of therapeutics. Here, we employ a synthetic host to simultaneously encapsulate an aromatic peptide and a non-canonical L-perfluorophenylalanine-containing peptide through embedded polar-π interactions, thus constructing an unprecedented series of heteropeptide dimers. To demonstrate the utility, this heteropeptide dimerization strategy was applied to achieve on-resin recognition of N-terminal aromatic residues in peptides as well as insulin, both exhibiting high recycling efficiency (> 95%). This research unveils a generic approach to exploit quantitative heteropeptide dimers for the design of supramolecular (bio)systems.