The production of atomically defined, uniform, large-area 2D materials remains as a challenge in materials chemistry. This approach enables the rapid discovery of biomimetic affinity reagents that combine the durability of synthetic materials with the specificity of biomolecular materials. This work demonstrates that key aspects of antibody structure and function – the creation of multivalent, combinatorial chemical diversity within a well-defined folded structure – can be realized with completely synthetic materials. These nanosheets were shown to be resistant to proteolytic degradation, and the binding to be dependent on the loop display density. Peptoid sequences were identified that bound to the heptameric protein, anthrax protective antigen, with high avidity and selectivity. These polyvalent, loop-functionalized nanosheets were screened using a homogeneous Förster resonance energy transfer (FRET) assay for binding to a variety of protein targets. Here we report the synthesis and screening of combinatorial libraries of sequence-defined peptoid polymers engineered to fold into ordered, supramolecular nanosheets displaying a high spatial density of more » diverse, conformationallyconstrained loops on their surface. Unfortunately, it remains a fundamental challenge to create a chemically-diverse population of protein-like, folded synthetic nanostructures with defined molecular conformations in water. However, the poor stability and high production cost of antibodies has prompted exploration of a variety of new, synthetic materials capable of specific molecular recognition. The ability of antibodies to bind a wide variety of analytes with high specificity and high affinity make them ideal candidates for therapeutic and diagnostic applications. These cell surface mimetic nanomaterials may find utility in the inactivation of pathogens or as selective molecular recognition elements. In all cases, evidence for multivalent binding was observed by systematic variation of the ligand display density on the nanosheet surface. Peptoid nanosheets were functionalized with more » globotriose, the natural ligand of Shiga toxin, and the effective binding of the nanomaterial was verified by the 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 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 Förster resonance energy transfer (FRET)-based binding assay. Both the linkers and the loops contained one alkyne-bearing monomer, to which different saccharides were attached by copper-catalyzed azide-alkyne cycloaddition reactions. The sugars were displayed using different linker lengths or within loops containing 2-6 hydrophilic peptoid monomers.
The constructs provide a highly organized 2D platform for recognition of carbohydrate-binding proteins. Here in this paper, 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. Multivalent interactions at the pathogen-cell interfaces govern binding events and can result in a strong and specific interaction. Their significance is particularly relevant in the recognition process between infectious pathogens (such as viruses, bacteria, toxins) and their host cells. Glycoproteins adhered on the cellular membrane play an important role in a wide range of cellular functions.
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