Orthogonal Halogen‐Bonding‐Driven 3D Supramolecular Assembly of Right‐Handed Synthetic Helical Peptides

Peptide‐mediated self‐assembly is a prevalent method for creating highly ordered supramolecular architectures. Herein, we report the first example of orthogonal C?X???X?C/C?X???π halogen bonding and hydrogen bonding driven crystalline architectures based on synthetic helical peptides bearing hybrids of l ‐sulfono‐γ‐AApeptides and natural amino acids. The combination of halogen bonding, intra‐/intermolecular hydrogen bonding, and intermolecular hydrophobic interactions enabled novel 3D supramolecular assembly. The orthogonal halogen bonding in the supramolecular architecture exerts a novel mechanism for the self‐assembly of synthetic peptide foldamers and gives new insights into molecular recognition, supramolecular design, and rational design of biomimetic structures.     

On the Role of Chirality in Guiding the Self‐Assembly of Peptides

Homochirality in peptides is crucial in sustaining “like–like” intermolecular interactions that allow the formation of assemblies and aggregates and is ultimately responsible for the resulting material properties. With the help of a series of stereoisomers of the tripeptide F–F–L, we demonstrate the critical role that peptide stereochemistry plays in the self‐assembly of peptides, guided by molecular recognition, and for self‐sorting. Homochiral self‐assemblies are thermally and mechanically more robust compared to heterochiral self‐assemblies. Morphological studies of the multicomponent peptide systems showed that aggregates formed from homochiral peptides possessed a uniform nano‐fibrous structure, whereas heterochiral systems resulted in self‐sorted systems with a heterogeneous morphology. In essence, homochiral peptides form the stronger aggregates, which may be one of reasons why homochirality is preferred in living systems.     

Controlled Supramolecular Self‐Assembly of Super‐charged β‐Lactoglobulin A–PEG Conjugates into Nanocapsules

The synthesis and characterization of a new protein–polymer conjugate composed of β lactoglobulin A (βLG A) and poly(ethylene glycol) PEG is described. βLG A was selectively modified to self‐assemble by super‐charging via amination or succinylation followed by conjugation with PEG. An equimolar mixture of the oppositely charged protein–polymer conjugates self‐assemble into spherical capsules of 80–100 nm in diameter. The self‐assembly proceeds by taking simultaneous advantage of the amphiphilicity and polyelectrolyte nature of the protein–polymer conjugate. These protein–polymer capsules or proteinosomes are reminiscent of protein capsids, and are capable of encapsulating solutes in their interior. We envisage this approach to be applicable to other globular proteins.