Yutong Wang,Lijun Yang,Mengfan Wang,Jiaxing Zhang,Wei Qi,Rongxin Su,Zhimin He
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.
Infectious diseases induced by pathogenic bacteria are the major causes for the failure of medical implants. Meanwhile, the drug-resistance is steadily developed because of the large and even inappropriate use of antibiotics. Therefore, the development of antibacterial coating with non-antibiotic-based agents on the surfaces of medical implants and devices has been an urgent need. Herein, we propose a bottlebrush-like antibacterial coating on a poly(styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS) triblock copolymer surface by UV-induced graft polymerization of poly(ethylene glycol) (PEG) acrylate terminated poly(lysine dendrimer). This PEG-conjugated antibacterial polymer possessed a substructure of α-helical backbone and cation dendrimer side chains stretching in the radial directions of the helix. The introduction of lysine peptide dendrimers endowed the prepared antibacterial polymer with precisely controlled characteristics of its local cation density, amphipathic composition as well as three-dimensional (3D) conformation to improve interactions with bacterial membranes. The antimicrobial assay and biocompatibility assay results showed that 96.83% of S. aureus and 99.99% of E. coli were killed after being in contact with the antibacterial coating, while no toxicity to mammalian cells or no hemolysis was detected. This antimicrobial activity was further confirmed by the molecular dynamics simulation results, which demonstrated that the employment of lysine peptide dendrimers enhanced the electrostatic interaction and hydrogen bonding between the brush and bacterial membranes remarkably. Such bottlebrush-like antibacterial coating constructed using α-helical peptide dendritic polymers may become an effective strategy for manufacturing antibacterial products for biomedical uses.
危险品化学品经营许可证（带存储）