Supramolecular Peptide Nanostructures Regulate Catalytic Efficiency and Selectivity.

Area of Science:

• Supramolecular Chemistry
• Biomaterials Science
• Catalysis

Background:

• Amphiphilic peptides can self-assemble into various nanostructures.
• Functionalized amino acids can impart specific properties to peptide assemblies.
• Understanding structure-function relationships in self-assembled systems is crucial for designing novel catalysts.

Purpose of the Study:

• To synthesize and characterize constitutionally isomeric tetrapeptides with S-aroylthiooxime (SATO) functionalized lysine residues.
• To investigate the self-assembly behavior of these peptides in aqueous solution.
• To evaluate the catalytic activity and efficiency of the resulting nanostructures in hydrolysis reactions.

Main Methods:

• Synthesis of tetrapeptides with glutamic acid, histidine, and SATO-lysine residues.
• Characterization of self-assembled nanostructures (nanoribbons, nanotoroids, nanocoils) using techniques like microscopy.
• Enzymatic assays to measure catalytic hydrolysis of model substrates.
• Coarse-grained molecular dynamics simulations and unsupervised machine learning for structural analysis.

Main Results:

• Three isomeric tetrapeptides self-assembled into distinct nanostructures: nanoribbons, a mixture of nanotoroids and nanoribbons, or nanocoils.
• All nanostructures exhibited catalytic activity for hydrolysis.
• Nanocoils demonstrated the highest rate enhancement and enzymatic efficiency.
• Molecular dynamics revealed histidine clusters in hydrophobic pockets of nanocoils, correlating with enhanced catalysis.
• Stereoselective hydrolysis of l-substrate was observed.

Conclusions:

• The order of amino acids in amphiphilic peptides significantly influences the resulting supramolecular nanostructure.
• Self-assembled peptide nanostructures can act as efficient catalysts.
• Histidine residue positioning within hydrophobic pockets is key to enhanced catalytic activity.
• This work provides insights into designing peptide-based nanomaterials for catalytic applications.