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 language | English (US) |
|---|---|
| Pages (from-to) | 821-829 |
| Number of pages | 9 |
| Journal | Nature nanotechnology |
| Volume | 12 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2017 |
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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
}
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.
In: Nature nanotechnology, Vol. 12, No. 8, 01.08.2017, p. 821-829.Research output: Contribution to journal › Article
TY - JOUR
T1 - Sulfated glycopeptide nanostructures for multipotent protein activation
AU - Lee, Sungsoo S.
AU - Fyrner, Timmy
AU - Chen, Feng
AU - Álvarez, Zaida
AU - Sleep, Eduard
AU - Chun, Danielle S.
AU - Weiner, Joseph A.
AU - Cook, Ralph W.
AU - Freshman, Ryan D.
AU - Schallmo, Michael S.
AU - Katchko, Karina M.
AU - Schneider, Andrew D.
AU - Smith, Justin T.
AU - Yun, Chawon
AU - Singh, Gurmit
AU - Hashmi, Sohaib Z.
AU - McClendon, Mark T.
AU - Yu, Zhilin
AU - Stock, Stuart R
AU - Hsu, Wellington K
AU - Hsu, Erin L
AU - Stupp, Samuel
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85026879563&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026879563&partnerID=8YFLogxK
U2 - 10.1038/nnano.2017.109
DO - 10.1038/nnano.2017.109
M3 - Article
VL - 12
SP - 821
EP - 829
JO - Nature Nanotechnology
JF - Nature Nanotechnology
SN - 1748-3387
IS - 8
ER -