Supramolecular Copolymers of Peptides and Lipidated Peptides and Their Therapeutic Potential

Supramolecular peptide chemistry offers a versatile strategy to create chemical systems useful as new biomaterials with potential to deliver nearly 1000 known candidate peptide therapeutics or integrate other types of bioactivity. We report here on the co-assembly of lipidated β-sheet-forming peptides with soluble short peptides, yielding supramolecular copolymers with various degrees of internal order. At low peptide concentrations, the co-monomer is protected by lodging within internal aqueous compartments and stabilizing internal β-sheets formed by the lipidated peptides. At higher concentrations, the peptide copolymerizes with the lipidated peptide and disrupts the β-sheet secondary structure. The thermodynamic metastability of the co-assembly in turn leads to the spontaneous release of peptide monomers and thus serves as a potential mechanism for drug delivery. We demonstrated the function of these supramolecular systems using a drug candidate for Alzheimer's disease and found that the copolymers enhance neuronal cell viability when the soluble peptide is released from the assemblies.