Glycosylated Peptoid Nanosheets as a Multivalent Scaffold for Protein Recognition

Abstract

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 Förster 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.

Design and preparation of organic nanomaterials using self‐assembled peptoids

“…Another example of the tunable applicability of peptoid nanosheets as molecular recognition systems was recently reported . The nanosheet surface was engineered to mimic the recognition properties of cell membranes, exploiting the ability of multivalent proteins to recognize their cellular target interacting with the sugars present on the cellular membrane.…”

Peptoids as tools and sensors

“…Battigelli et al . demonstrated an approach to mimic the construction and function of cell‐surface saccharide ligand presentation using peptoid nanosheets.…”

Linking two worlds in polymer chemistry: The influence of block uniformity and dispersity in amphiphilic block copolypeptoids on their self‐assembly

“…developed a method to produce uniform and sequence‐defined peptoids, the solid‐phase submonomer synthesis (SPSS) . This method opened a broad range of designs of molecules that self‐assemble into well‐defined structures with higher orders, for example crystalline, three‐dimensional nanotubes with tunable diameters or nanosheets with lateral dimensions in the μm‐scale with the potential to selectively bind to multivalent proteins or viruses . These hierarchical structures can assemble due to a rather complex and strictly defined sequence and/or exact chain‐length.…”