Histidine-Based Supramolecular Nanoassembly Exhibiting Dual Enzyme-Mimetic Functions: Altering the Tautomeric Preference of Histidine to Tailor Oxidative/Hydrolytic Catalysis

• Published in: Nano letters Vol. 23; no. 24; pp. 11461 - 11468
• Main Authors: Du, Peidong, Xu, Shichao, Wu, Haifeng, Liu, Yuanxi, Wang, Zhen-Gang
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.12.2023
• Subjects: Biomimetics; Catalysis; Copper; Histidine - chemistry; Hydrolysis; Nitrogen; Oxidative Stress; self-assembly; histidine; enzyme mimic; biocatalysis; tautomeric preference
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/acs.nanolett.3c02934

Challenges persist in replicating enzyme-like active sites with functional group arrangements in supramolecular catalysis. In this study, we present a supramolecular material comprising Fmoc-modified histidine and copper. We also investigated the impact of noncanonical amino acids (δmH and εmH), isomers of histidine, on the catalytic process. The Fmoc-δmH-based nanoassembly exhibits an approximately 15-fold increase in oxidative activity and an ∼50-fold increase in hydrolytic activity compared to Fmoc-εmH (k cat/K m). This distinction arises from differences in basicity and ligation properties between the ε- and δ-nitrogen of histidine. The addition of guanosine monophosphate further enhances the oxidative activity of the histidine- and methylated histidine-based catalysts. The Fmoc-δmH/Cu2+-based nanoassembly catalyzes the oxidation/hydrolysis cascade of 2′,7′-dichlorofluorescein diacetate, benefiting from the synergistic effect between the copper center and the nonligating ε-nitrogen of histidine. These findings advance the biomimetic catalyst design and provide insights into the mechanistic role of essential residues in natural systems.