Bioinspired Supramolecular Catalysts from Designed Self-Assembly of DNA or Peptides

Abstract

Enzymes play vital roles in cellular functions by catalyzing biochemical reactions in high activity and selectivity, which is largely attributed to the cooperation between the exquisitely distributed functional groups at the active sites. Reconstruction of the enzymatic active sites in the artificial systems, to produce active and robust biocatalysts, has been a significant but challenging subject. Biomolecular self-assembly, typically with de novo designed peptide or DNA as the building blocks, provides an effective avenue to orient and confine reactive groups into a catalytically active configuration to mimic and even rival the catalytic performance of native enzymes. In this Review, we discuss the chemical and structural properties of DNA and peptide selfassemblies, and principles and strategies of designing active sites that show hydrolase-, peroxidase-, oxidase-, or aldolase-like activities. We focus on the relationship between and control over the structures of the artificial active sites and catalytic performances. We also highlight the synergies between the components in the formation of the active sites, as well as the applications of the artificial enzymes. In the end, we provide an outlook on the obstacles, possible solutions, and future directions, in the aspect of structural modeling, improving catalytic performances, and upgrading complexity of the active sites.

DNA-based enzymatic systems and their applications

“…also proposed that the embedded external quartet was in favor of the enhanced affinity to hemin and activation of the iron atom in hemin ( Wang et al., 2020 ). Moreover, the addition of histidine-rich peptides can also contribute to enhanced enzymatic activity ( Liu et al., 2017b , 2020b ; Du et al., 2021 , 2022 ), as is shown in Figure 2 C. Van der Waals force drives histidine-rich peptides to assemble with G-rich Dzs for capturing hemin. The stacking state of hemin presented at the terminals of folded G-rich Dzs allows more hemins to be exposed to H 2 O 2 , resulting in the enhanced catalytic activity.…”

A Self‐Assembled Fmoc‐Diphenylalanine Hydrogel‐Encapsulated Pt Nanozyme as Oxidase‐ and Peroxidase‐Like Breaking pH Limitation for Potential Antimicrobial Application

“…As a carrier, Fmoc‐based hydrogel with inherent antibacterial properties can effectively encapsulate various nanozymes to achieve synergistic sterilization. On the other hand, inspired by the structure of a natural enzyme composed of an active center and amino acids, and the catalytic function of a natural enzyme largely depends on the chemical structure of the active site [24] . Combining Fmoc‐based hydrogels with nanozymes may be useful for mimicking natural enzymes and improving function.…”

Photo-Fenozyme Nanoparticles Based on Fe(II)-Coordination-Driven Cyanine-Based Amino Acid Assembly for Photodynamic Ferrotherapy

“…Naturally occurring enzymes have become increasingly prevalent in reactive oxygen species-mediated ferrotherapy. , However, the inherently low stability of the enzyme and restricted bioreaction are major limitations for increasing ferrotherapy efficiency. − Nanozymes with enzyme-mimicking properties, due to their scalability, stability, and chemical diversity motivate scientists to develop efficient nanozyme-based ferrotherapeutic agents. Simultaneously, oxidoreductases-like nanomaterials including metal–organic complexes, , polymer micelles/dendrimers, and inorganic nanoparticles have been successfully developed to modulate reactive oxygen species in cancer therapy .…”