Covalent Linkage and Macrocylization Preserve and Enhance Synergistic Interactions in Catalytic Amyloids.

The self-assembly of short peptides into catalytic amyloid-like nanomaterials has proven to be a powerful tool in both understanding the evolution of early proteins and identifying new catalysts for practically useful chemical reactions. Here we demonstrate that both parallel and antiparallel arrangements of ß-sheets can accommodate metal ions in catalytically productive coordination environments. Moreover, synergistic relationships, identified in catalytic amyloid mixtures, can be captured in macrocyclic and sheet-loop-sheet species, that offer faster rates of assembly and provide more complex asymmetric arrangements of functional groups, thus paving the way for future designs of amyloid-like catalytic proteins. Our findings show how initial catalytic activity in amyloid assemblies can be propagated and improved in more-complex molecules, providing another link in a complex evolutionary chain between short, potentially abiotically produced peptides and modern-day enzymes.

Synergistic Interactions Are Prevalent in Catalytic Amyloids.

Interactions between multiple functional groups are key to catalysis. Previously, we reported synergistic interactions in catalytic amyloids formed by mixtures of heptameric peptides that lead to significant improvements in esterase activity. Herein, we describe the in-depth investigation of synergistic interactions within a family of amyloid fibrils, exploring the results of functional group interactions, the effects of chirality and the use of mixed enantiomers within fibrils. Remarkably, we find that synergistic interactions (either positive or negative) are found in the vast majority of binary mixtures of catalytic amyloid-forming peptides. The productive arrangements of functionalities rapidly identified by mixing different peptides will undoubtedly lead to the development of more active catalysts for a variety of different transformations.