Enzyme-Mimicking Materials from Designed Self-Assembly of Lysine-Rich Peptides and G‑Quadruplex DNA/Hemin DNAzyme: Charge Effect of the Key Residues on the Catalytic Functions

• Published in: Biomacromolecules Vol. 23; no. 8; pp. 3469 - 3476
• Main Authors: Sun, Hao, Wu, Haifeng, Teng, Qiao, Liu, Yuanxi, Wang, Hui, Wang, Zhen-Gang
• Format: Journal Article
• Language: English
• Published: American Chemical Society 08.08.2022
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.2c00620

In enzymatic active sites, the essential functional groups are spatially arranged as a result of the enzyme three-dimensional 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 H2O2 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 ε-polylysine/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 NH2 behaved like a base catalyst, similar to His-42 residue in the natural heme pocket, while the protonated NH3 + 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.