Session: General Catalysis:

Enzymes play vital roles in catalyzing biochemical reactions with high activity and selectivity, which is largely attributed to the delicate 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. Inspired by the abundant helical structure in the catalytic center of natural phosphatases, we constructed 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 that can only hydrolyze carboxylic ester bond, we emphasized the significance of helical structure in the hydrolysis of phosphoester bonds (over 1000 folds higher in catalytic efficiency). Structure–activity relationship revealed that the phosphatase-like function attributed to the unique helical dipole moment for substrate binding as well as the supramolecular assembly for the catalytic center formation. Moreover, we verified the feasibility of these functional helical species as a potential substitute for adenosine triphosphatase (ATPase) and alkaline phosphatase (ALPase) in specific biological processes. This work not only presents a new approach for the construction of artificial enzymes through simple peptide modules, but also provides a model for primitive enzymes formed from helical short peptides self-assemblies.

Mengfan Wang

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