Supramolecular Recognition and Selective Protein Uptake by Peptide Hybrids

The intracellular transport of exogenous proteins has emerged as one of the most promising methodologies for biotechnology and chemical biology. Currently, protein delivery is mainly achieved by liposome encapsulation, translational fusion, and ionic/hydrophobic non‐covalent aggregation with transporting molecular vehicles. This work introduces the concept of supramolecular recognition and selective transport of proteins by peptide hybrid materials. A helical amphiphilic cationic peptide that bears two orthogonal alkoxyamines for the precise anchoring of protein ligands has been designed. After the attachment of these protein ligands, the peptide showed a high binding affinity for its target protein (i.e., mannose/Concanavalin A, Biotin/Streptavidin). The resulting peptide/protein hybrids were taken up by human cells such as HeLa and HepG2. The concept described in this manuscript could potentially be adapted, through the appropriate choice of ligands, to the transport of other proteins with suitable supramolecular binding motifs. Peptide/protein hybrids are reported for the selective recognition and translocation of model proteins such as Concanavalin A and Streptavidin. This method could potentially be adapted, through the appropriate choice of ligands, to the transport of other proteins with suitable supramolecular binding motifs.