On-Resin Recognition of Aromatic Oligopeptides and Proteins through Host-Enhanced Heterodimerization
Xiaoyi Chen, Zehuan Huang, Renata L. Sala, Alan McLean, Guanglu Wu, Kamil Sokołowski, Katie King, Jade A. McCune, Oren A. Scherman
Abstract
High Resolution Image Download MS PowerPoint Slide Peptide dimerization is ubiquitous in natural protein conjugates and artificial self-assemblies. A major challenge in artificial systems remains achieving quantitative peptide heterodimerization, critical for next-generation biomolecular purification and formulation of therapeutics. Here, we employ a synthetic host to simultaneously encapsulate an aromatic and a noncanonical l -perfluorophenylalanine-containing peptide through embedded polar−π interactions, constructing an unprecedented series of heteropeptide dimers. To demonstrate the utility, this heteropeptide dimerization strategy was applied toward 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.