pH-Responsive Self-Assembly of Amyloid Fibrils for Dual Hydrolase-Oxidase Reactions

Abstract

There is an increasing interest in synthetic systems that can execute bio-inspired chemical reactions without requiring the complex structures that characterize enzymes in their components.The hierarchical self-assembly of peptides provides a means to create catalytic microenvironments. Ideally, as it occurs in enzymes, the catalytic activity of peptide nanostructures should be reversibly regulated. In a typical enzyme mimetic design, the peptide's self-assembling and catalytic activities are segregated into different regions of the sequence. Here, we aimed to design minimal peptides in which the self-assembly and function were all encoded in the same amino acids. Moreover, we wanted to endorse the resulting one-component nanomaterial with divergent, chemically unrelated, catalytic activities, a property not observed in natural enzymes. We show that short peptides consisting only of histidine and tyrosine residues, arranged in a binary pattern, form biocompatible amyloid-like fibrils and hydrogels combining hydrolytic and electrocatalytic activities. The nanofibers' mesoscopic properties are controlled by pH, the transition between assembled active b-sheet fibrils, and disassembled inactive random coil species occurring in a physiologically relevant pH range. The structure of one of such amyloid-like fibrils, as derived from molecular dynamic simulations, provides insights on how they attain this unique combination of structural and catalytic properties.

Prion‐like proteins: from computational approaches to proteome‐wide analysis

“…This is important not only because they will allow us to deep into the biology of the prion‐like proteins but also for their potential therapeutical and nanotechnological implications. In this last respect, the knowledge we have gained from proteome‐wide analyses has already crystallized in the development of new nanomaterials with fascinating functional properties [130,131] that would have never seen the light without the herein described bioinformatic analysis.…”

“…In this last respect, the knowledge we have gained from proteome-wide analyses has already crystallized in the development of new nanomaterials with fascinating functional properties [131,132] that would have never seen the light without the herein described bioinformatic analysis. original.…”

Amyloids as Building Blocks for Macroscopic Functional Materials: Designs, Applications and Challenges

“…Spatially organizing multiple histidine side chains into close proximity by controlled amyloid assembly can promote esterase activity. Diaz-Caballero et al designed such a peptide using only histidine and tyrosine (HYHYHYHY), which self-assembled into cross-β fibrils ( Figure 6 ) [ 142 ]. Tyrosine residues promoted the self-assembly of the peptide into nanofibrils while also displaying oxidase activity.…”

“…The self-assembled HYHYHYHY fibrils provided important microenvironments for histidine and tyrosine sidechain to exhibit esterase (A) and oxidase (B) activities, respectively. Reprinted with permission [ 142 ]. Copyright 2020, American Chemical Society.…”

Catalytic Amyloids as Novel Synthetic Hydrolases

“…Interestingly, fully polar peptides with sequences alternating glutamine and tyrosine result in the formation of amyloids in vitro that are stabilized by aromatic interactions [49]. Replacing all glutamines with histidine in these small peptides charges the resulting self-assembled amyloid-like peptides with metal-independent esterase catalytic activity [50]. Given the very few reports available so far on metal-independent catalytic amyloids with hydrolase activities, it is difficult to speculate on whether these amyloids operate through a common enzyme-like mechanism.…”