Supramolecular Recognition and Selective Protein Uptake by Peptide Hybrids

Abstract

The intracellular transport of exogenous proteins has emerged as one of the most promising methodologies for biotechnology and chemical biology. Current protein delivery is mainly approached by liposome encapsulation, translational fusion and ionic/hydrophobic non‐covalent aggregation with transporting molecular vehicles. We here introduce the concept of supramolecular recognition and selective transport of proteins by peptide hybrid materials. We have designed a helical amphiphilic cationic peptide that bears two orthogonal alkoxyamines for the precise anchoring of protein ligands. After the attachment of these protein ligands, the peptide showed a high binding affinity for its protein target (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