No abstract

Enzymes fold into unique three-dimensional structures to distribute their reactive amino acid residues, but environmental changes can disrupt their essential folding and lead to irreversible activity loss. The de novo synthesis of enzyme-like active sites is challenging due to the difficulty of replicating the spatial arrangement of functional groups. Here, we present a supramolecular mimetic enzyme formed by self-assembling nucleotides with fluorenylmethyloxycarbonyl (Fmoc)-modified amino acids and copper. This catalyst exhibits catalytic functions akin those of copper cluster-dependent oxidases, and catalytic performance surpasses to date-reported artificial complexes. Our experimental and theoretical results reveal the crucial role of periodic arrangement of amino acid components, enabled by fluorenyl stacking, in forming oxidase-mimetic copper clusters. Nucleotides provide coordination atoms that enhance copper activity by facilitating the formation of a copper-peroxide intermediate. The catalyst shows thermophilic behavior, remaining active up to 95 °C in an aqueous environment. These findings may aid the design of advanced biomimetic catalysts and offer insights into primordial redox enzymes.

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Photodynamic therapy (PDT) is a light triggered therapy by producing reactive oxygen species (ROS), but traditional PDT may suffer from the real‐time illumination that reduces the compliance of treatment and cause phototoxicity. A supramolecular photoactive G‐quartet based material is reported, which is self‐assembled from guanosine (G) and 4‐formylphenylboronic acid/1,8‐diaminooctane, with incorporation of riboflavin as a photocatalyst to the G4 nanowire, for post‐irradiation photodynamic antibacterial therapy. The G4‐materials, which exhibit hydrogel‐like properties, provide a scaffold for loading riboflavin, and the reductant guanosine for the riboflavin for phototriggered production of the therapeutic H2O2. The photocatalytic activity shows great tolerance against room temperature storage and heating/cooling treatments. The riboflavin‐loaded G4 hydrogels, after photo‐irradiation, are capable of killing gram‐positive bacteria (e.g., Staphylococcus aureus), gram‐negative bacteria (e.g., Escherichia coli), and multidrug resistant bacteria (methicillin‐resistant Staphylococcus aureus) with sterilization ratio over 99.999%. The post‐irradiated hydrogels also exhibit great antibacterial activity in the infected wound of the rats, revealing the potential of this novel concept in the light therapy.

In enzymatic active sites, the essential functional groups are spatially arranged as a result of the enzyme threedimensional folding, which leads to remarkable catalytic properties. We are inspired to self-assemble the polylysine peptides with guanine-rich DNA and hemin as cofactor to fabricate the peroxidase-mimicking catalytic nanomaterials. The DNA can fold into G-quadruplex to provide a supramolecular scaffold and a nucleobase for supporting and coordinating hemin, and the polylysine provides amine as distal groups to promote the H 2 O 2 adsorption to the iron of hemin. The polylysine and DNA components synergistically accelerated the hemin-catalyzed reactions, and the complex containing ε-polylysine exhibited higher activity than α-polylysine. This activity difference is attributed to the higher pK a value and more susceptible protonation of amine of ε-polylysine than α-polylysine. The εpolylysine/DNA/hemin had similar coordination states of hemin and conformations of the components to α-polylysine/DNA/ hemin but accelerated the formation of the intermediate compound I faster than α-polylysine. Theoretical simulation reveals that the unprotonated NH 2 behaved like a base catalyst, similar to His-42 residue in the natural heme pocket, while the protonated NH 3 + acted as an acid, which indicated that the base catalyst on the distal side of the hemin pocket is more active than the acid. This work provides an avenue to control the distribution of the catalytic residues in an enzyme-like active site and to understand the roles of the key residues of native enzymes.