Sulfated glycopeptide nanostructures for multipotent protein activation

Sungsoo S. Lee, Timmy Fyrner, Feng Chen, Zaida Álvarez, Eduard Sleep, Danielle S. Chun, Joseph A. Weiner, Ralph W. Cook, Ryan D. Freshman, Michael S. Schallmo, Karina M. Katchko, Andrew D. Schneider, Justin T. Smith, Chawon Yun, Gurmit Singh, Sohaib Z. Hashmi, Mark T. McClendon, Zhilin Yu, Stuart R. Stock, Wellington K. Hsu & 2 others Erin L. Hsu, Samuel I Stupp

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.

Original languageEnglish
Pages (from-to)821-829
Number of pages9
JournalNature Nanotechnology
Volume12
Issue number8
DOIs
Publication statusPublished - Aug 1 2017

Fingerprint

Glycopeptides
Nanostructures
Chemical activation
activation
proteins
Proteins
polysaccharides
Polysaccharides
bones
Bone
Bone Morphogenetic Protein 2
heparins
Monosaccharides
monosaccharides
Biological systems
animal models
spine
Set theory
activity (biology)
Heparin

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrical and Electronic Engineering

Cite this

Lee, S. S., Fyrner, T., Chen, F., Álvarez, Z., Sleep, E., Chun, D. S., ... Stupp, S. I. (2017). Sulfated glycopeptide nanostructures for multipotent protein activation. Nature Nanotechnology, 12(8), 821-829. https://doi.org/10.1038/nnano.2017.109

Sulfated glycopeptide nanostructures for multipotent protein activation. / Lee, Sungsoo S.; Fyrner, Timmy; Chen, Feng; Álvarez, Zaida; Sleep, Eduard; Chun, Danielle S.; Weiner, Joseph A.; Cook, Ralph W.; Freshman, Ryan D.; Schallmo, Michael S.; Katchko, Karina M.; Schneider, Andrew D.; Smith, Justin T.; Yun, Chawon; Singh, Gurmit; Hashmi, Sohaib Z.; McClendon, Mark T.; Yu, Zhilin; Stock, Stuart R.; Hsu, Wellington K.; Hsu, Erin L.; Stupp, Samuel I.

In: Nature Nanotechnology, Vol. 12, No. 8, 01.08.2017, p. 821-829.

Research output: Contribution to journalArticle

Lee, SS, Fyrner, T, Chen, F, Álvarez, Z, Sleep, E, Chun, DS, Weiner, JA, Cook, RW, Freshman, RD, Schallmo, MS, Katchko, KM, Schneider, AD, Smith, JT, Yun, C, Singh, G, Hashmi, SZ, McClendon, MT, Yu, Z, Stock, SR, Hsu, WK, Hsu, EL & Stupp, SI 2017, 'Sulfated glycopeptide nanostructures for multipotent protein activation', Nature Nanotechnology, vol. 12, no. 8, pp. 821-829. https://doi.org/10.1038/nnano.2017.109
Lee SS, Fyrner T, Chen F, Álvarez Z, Sleep E, Chun DS et al. Sulfated glycopeptide nanostructures for multipotent protein activation. Nature Nanotechnology. 2017 Aug 1;12(8):821-829. https://doi.org/10.1038/nnano.2017.109
Lee, Sungsoo S. ; Fyrner, Timmy ; Chen, Feng ; Álvarez, Zaida ; Sleep, Eduard ; Chun, Danielle S. ; Weiner, Joseph A. ; Cook, Ralph W. ; Freshman, Ryan D. ; Schallmo, Michael S. ; Katchko, Karina M. ; Schneider, Andrew D. ; Smith, Justin T. ; Yun, Chawon ; Singh, Gurmit ; Hashmi, Sohaib Z. ; McClendon, Mark T. ; Yu, Zhilin ; Stock, Stuart R. ; Hsu, Wellington K. ; Hsu, Erin L. ; Stupp, Samuel I. / Sulfated glycopeptide nanostructures for multipotent protein activation. In: Nature Nanotechnology. 2017 ; Vol. 12, No. 8. pp. 821-829.
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