Glycosylated Peptoid Nanosheets as a Multivalent Scaffold for Protein Recognition

Alessia Battigelli, Jae Hong Kim, Dilani C. Dehigaspitiya, Caroline Proulx, Ellen J. Robertson, Daniel J. Murray, Behzad Rad, Kent Kirshenbaum, Ronald N. Zuckermann

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2455-2465
Number of pages11
JournalACS Nano
Volume12
Issue number3
DOIs
StatePublished - Mar 27 2018

Fingerprint

Peptoids
Nanosheets
Scaffolds (biology)
Scaffolds
carbohydrates
proteins
Proteins
Pathogens
pathogens
Shiga Toxin
Alkynes
Ligands
Carbohydrates
Nanostructured materials
Sugars
Energy transfer
alkynes
sugars
Assays
cells

Keywords

  • bioinspired polymers
  • cell-surface mimetics
  • molecular recognition
  • multivalent binding
  • Protein-mimetic materials
  • two-dimensional nanomaterials

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Battigelli, A., Kim, J. H., Dehigaspitiya, D. C., Proulx, C., Robertson, E. J., Murray, D. J., ... Zuckermann, R. N. (2018). Glycosylated Peptoid Nanosheets as a Multivalent Scaffold for Protein Recognition. ACS Nano, 12(3), 2455-2465. https://doi.org/10.1021/acsnano.7b08018

Glycosylated Peptoid Nanosheets as a Multivalent Scaffold for Protein Recognition. / Battigelli, Alessia; Kim, Jae Hong; Dehigaspitiya, Dilani C.; Proulx, Caroline; Robertson, Ellen J.; Murray, Daniel J.; Rad, Behzad; Kirshenbaum, Kent; Zuckermann, Ronald N.

In: ACS Nano, Vol. 12, No. 3, 27.03.2018, p. 2455-2465.

Research output: Contribution to journalArticle

Battigelli, A, Kim, JH, Dehigaspitiya, DC, Proulx, C, Robertson, EJ, Murray, DJ, Rad, B, Kirshenbaum, K & Zuckermann, RN 2018, 'Glycosylated Peptoid Nanosheets as a Multivalent Scaffold for Protein Recognition', ACS Nano, vol. 12, no. 3, pp. 2455-2465. https://doi.org/10.1021/acsnano.7b08018
Battigelli A, Kim JH, Dehigaspitiya DC, Proulx C, Robertson EJ, Murray DJ et al. Glycosylated Peptoid Nanosheets as a Multivalent Scaffold for Protein Recognition. ACS Nano. 2018 Mar 27;12(3):2455-2465. https://doi.org/10.1021/acsnano.7b08018
Battigelli, Alessia ; Kim, Jae Hong ; Dehigaspitiya, Dilani C. ; Proulx, Caroline ; Robertson, Ellen J. ; Murray, Daniel J. ; Rad, Behzad ; Kirshenbaum, Kent ; Zuckermann, Ronald N. / Glycosylated Peptoid Nanosheets as a Multivalent Scaffold for Protein Recognition. In: ACS Nano. 2018 ; Vol. 12, No. 3. pp. 2455-2465.
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