Bioinspired Phosphatase-like Mimic Built from the Self-Assembly of De Novo Designed Helical Short Peptides

Enzymes play vital roles in catalyzing biochemical reactions with high activity and selectivity, which is largely attributed to the delicately organized structure and groups at catalytic domains. Reconstruction of the enzymatic catalytic domains in artificial systems, to produce enzyme-like mimic, has become an attractive but challenging subject. Herein, inspired by the helical structure in the catalytic center of natural phosphatases, we created a phosphatase-like mimic through the self-assembly of de novo designed helical heptapeptides. The helical heptapeptides were elaborately decorated with well-studied catalytic groups and exhibited obvious phosphatase-like catalytic activity upon hierarchically self-assembling. In comparison with β-sheet-organized peptide assemblies, we emphasized the significance of helical structure in the hydrolysis of phosphoester bonds (over 1000 times higher in catalytic efficiency). The structure–activity relationship reveals that the phosphatase-like function attributed to the specific helical dipole moment for the binding of substrates as well as the supramolecular assembly for the formation of catalytic center. Moreover, we verified the feasibility of these helical species as a potential substitute for adenosine triphosphatase (ATPase) and alkaline phosphatase (ALPase) in some specific biological processes. This work not only presents an approach for the construction of artificial enzymes with simple peptide modules but also provides a model for primitive enzymes formed from helical short peptides that relied on self-assembly to achieve a folded structure.