Tunable, biodegradable grafting-from glycopolypeptide bottlebrush polymers

Zachary S Clauss; Casia L Wardzala; Austin E Schlirf; Nathaniel S Wright; Simranpreet S Saini; Bibiana Onoa; Carlos Bustamante; Jessica R Kramer

doi:10.1038/s41467-021-26808-5

Tunable, biodegradable grafting-from glycopolypeptide bottlebrush polymers

Nat Commun. 2021 Nov 9;12(1):6472. doi: 10.1038/s41467-021-26808-5.

Authors

Zachary S Clauss¹, Casia L Wardzala¹, Austin E Schlirf¹, Nathaniel S Wright¹, Simranpreet S Saini¹, Bibiana Onoa², Carlos Bustamante^{2

3

4

5

6

7}, Jessica R Kramer^{8

9}

Affiliations

¹ Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, 84102, USA.
² Howard Hughes Medical Institute University of California Berkeley, Berkeley, CA, 94720, USA.
³ Department of Chemistry, University of California Berkeley, Berkeley, CA, 94720, USA.
⁴ Institute for Quantitative Biosciences, University of California, Berkeley, CA, 94720, USA.
⁵ Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
⁶ Department of Physics, University of California Berkeley, Berkeley, CA, 94720, USA.
⁷ Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, 94720, USA.
⁸ Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, 84102, USA. jessica.kramer@utah.edu.
⁹ Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, 84102, USA. jessica.kramer@utah.edu.

Abstract

The cellular glycocalyx and extracellular matrix are rich in glycoproteins and proteoglycans that play essential physical and biochemical roles in all life. Synthetic mimics of these natural bottlebrush polymers have wide applications in biomedicine, yet preparation has been challenged by their high grafting and glycosylation densities. Using one-pot dual-catalysis polymerization of glycan-bearing α-amino acid N-carboxyanhydrides, we report grafting-from glycopolypeptide brushes. The materials are chemically and conformationally tunable where backbone and sidechain lengths were precisely altered, grafting density modulated up to 100%, and glycan density and identity tuned by monomer feed ratios. The glycobrushes are composed entirely of sugars and amino acids, are non-toxic to cells, and are degradable by natural proteases. Inspired by native lipid-anchored proteoglycans, cholesterol-modified glycobrushes were displayed on the surface of live human cells. Our materials overcome long-standing challenges in glycobrush polymer synthesis and offer new opportunities to examine glycan presentation and multivalency from chemically defined scaffolds.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Extracellular Matrix / metabolism
Glycosylation
Humans
Macromolecular Substances / chemistry
Macromolecular Substances / metabolism*
Polymerization
Polymers / chemistry
Polymers / metabolism*
Proteoglycans / metabolism

Substances

Macromolecular Substances
Polymers
Proteoglycans