期刊
ACS NANO
卷 12, 期 3, 页码 2455-2465出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.7b08018
关键词
protein-mimetic materials; molecular recognition; multivalent binding; two-dimensional nanomaterials; bioinspired polymers; cell-surface mimetics
类别
资金
- Defense Threat Reduction Agency [DTRA10027-15875]
- DARPA Fold F(x) program
- Advanced Light Source at Lawrence Berkeley National Laboratory
- Office of Science, Office of Basic Energy Sciences, U.S. Department of Energy [DEAC02-05CH11231]
- National Research Foundation (NRF) by Korean government [NRF-2016R1A6A3A03007606]
Glycoproteins adhered on the cellular membrane play a pivotal role in a wide range of cellular functions. Their importance is particularly relevant in the recognition process between infectious pathogens (such as viruses, bacteria, toxins) and their host cells. Multivalent interactions at the pathogen-cell interfaces govern binding events and can result in a strong and specific interaction. Here we report an approach to mimic the cell surface presentation of carbohydrate ligands by the multivalent display of sugars on the surface of peptoid nanosheets. The constructs provide a highly organized 2D platform for recognition of carbohydrate-binding proteins. The sugars were displayed using different linker lengths or within loops containing 2-6 hydrophilic peptoid monomers. Both the linkers and the loops contained one alkyne-bearing monomer, to which different saccharides were attached by copper-catalyzed azide-alkyne cycloaddition reactions. Peptoid nanosheets functionalized with different saccharide groups were able to selectively bind multivalent lectins, Concanavalin A and Wheat Germ Agglutinin, as observed by fluorescence microscopy and a homogeneous Forster resonance energy transfer (FRET)-based binding assay. To evaluate the potential of this system as sensor for threat agents, the ability of functionalized peptoid nanosheets to bind Shiga toxin was also studied. Peptoid nanosheets were functionalized with globotriose, the natural ligand of Shiga toxin, and the effective binding of the nanomaterial was verified by the FRET-based binding assay. In all cases, evidence for multivalent binding was observed by systematic variation of the ligand display density on the nanosheet surface. These cell surface mimetic nanomaterials may find utility in the inactivation of pathogens or as selective molecular recognition elements.
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