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Title: Sulfated glycopeptide nanostructures for multipotent protein activation

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. Here, we report on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with very 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 signaling 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 expected. These super-bioactive nanostructures may enable many therapies in the horizon involving proteins.

Authors:
 [1];  [2];  [2];  [2];  [2];  [3];  [3];  [3];  [3];  [3];  [3];  [3];  [3];  [3];  [3];  [3];  [2];  [2];  [4];  [5] more »;  [5];  [6] « less
  1. Stanford Univ., CA (United States). School of Medicine, Blau Lab., and Baxter Lab. for Stem Cell Biology; Northwestern Univ., Evanston, IL (United States). Simpson Querrey Inst. for BioNanotechnology and Dept. of Materials Science and Engineering
  2. Northwestern Univ., Evanston, IL (United States). Simpson Querrey Inst. for BioNanotechnology
  3. Northwestern Univ., Evanston, IL (United States). Dept. of Orthopaedic Surgery
  4. Northwestern Univ., Evanston, IL (United States). Dept. of Molecular Pharmacology and Biological Chemistry
  5. Northwestern Univ., Evanston, IL (United States). Simpson Querrey Inst. for BioNanotechnology and Dept. of Orthopaedic Surgery
  6. Northwestern Univ., Evanston, IL (United States). Simpson Querrey Inst. for BioNanotechnology, Dept. of Materials Science and Engineering, Dept. of Biomedical Engineering, Dept. of Chemistry and Dept. of Medicine
Publication Date:
Research Org.:
Energy Frontier Research Centers (EFRC) (United States). Center for Bio-Inspired Energy Science (CBES); Northwestern Univ., Evanston, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institutes of Health (NIH); Samsung Scholarship
Contributing Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Univ. of Chicago, IL (United States); Würzburg Univ. (Germany); Univ. of California, Irvine, CA (United States); Washington Univ., Saint Louis, MO (United States)
OSTI Identifier:
1463097
Grant/Contract Number:  
SC0000989; 5R01DE015920-10; FG02-00ER45810
Resource Type:
Accepted Manuscript
Journal Name:
Nature Nanotechnology
Additional Journal Information:
Journal Volume: 12; Journal Issue: 8; Journal ID: ISSN 1748-3387
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 77 NANOSCIENCE AND NANOTECHNOLOGY

Citation Formats

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., and Stupp, Samuel I. Sulfated glycopeptide nanostructures for multipotent protein activation. United States: N. p., 2017. Web. doi: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. United States. doi: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., and Stupp, Samuel I. Mon . "Sulfated glycopeptide nanostructures for multipotent protein activation". United States. doi:10.1038/NNANO.2017.109. https://www.osti.gov/servlets/purl/1463097.
@article{osti_1463097,
title = {Sulfated glycopeptide nanostructures for multipotent protein activation},
author = {Lee, Sungsoo S. and Fyrner, Timmy and Chen, Feng and Álvarez, Zaida and Sleep, Eduard and Chun, Danielle S. and Weiner, Joseph A. and Cook, Ralph W. and Freshman, Ryan D. and Schallmo, Michael S. and Katchko, Karina M. and Schneider, Andrew D. and Smith, Justin T. and Yun, Chawon and Singh, Gurmit and Hashmi, Sohaib Z. and McClendon, Mark T. and Yu, Zhilin and Stock, Stuart R. and Hsu, Wellington K. and Hsu, Erin L. and Stupp, Samuel I.},
abstractNote = {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. Here, we report on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with very 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 signaling 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 expected. These super-bioactive nanostructures may enable many therapies in the horizon involving proteins.},
doi = {10.1038/NNANO.2017.109},
journal = {Nature Nanotechnology},
number = 8,
volume = 12,
place = {United States},
year = {2017},
month = {6}
}

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Works referenced in this record:

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