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Stereochemical Control Yields Mucin Mimetic Polymers
Name
acscentsci.0c01569.pdf
Description
Published version
Size
3.28 MB
Format
Adobe PDF
Checksum (MD5)
20042bb99bbb21f9e1133a835180f9c8
Author(s)
Kruger, Austin G
Brucks, Spencer D
Yan, Tao
Cárcarmo-Oyarce, Gerardo
Wei, Yuan
Wen, Deborah H
Carvalho, Dayanne R
Hore, Michael JA
Ribbeck, Katharina
Schrock, Richard R
Date Issued
2021
Journal
ACS Central Science
Publisher
American Chemical Society (ACS)
Version
Final published version
Abstract
All animals except sponges produce mucus. Across the animal kingdom, this hydrogel mediates surface wetting, viscosity, and protection against microbes. The primary components of mucus hydrogels are mucins-high molecular weight O-glycoproteins that adopt extended linear structures. Glycosylation is integral to mucin function, but other characteristics that give rise to their advantageous biological activities are unknown. We postulated that the extended conformation of mucins is critical for their ability to block microbial virulence phenotypes. To test this hypothesis, we developed synthetic mucin mimics that recapitulate the dense display of glycans and morphology of mucin. We varied the catalyst in a ring-opening metathesis polymerization (ROMP) to generate substituted norbornene-derived glycopolymers containing either cis- or trans-alkenes. Conformational analysis of the polymers based on allylic strain suggested that cis- rather than trans-poly(norbornene) glycopolymers would adopt linear structures that mimic mucins. High-resolution atomic force micrographs of our polymers and natively purified Muc2, Muc5AC, and Muc5B mucins revealed that cis-polymers adopt extended, mucin-like structures. The cis-polymers retained this structure in solution and were more water-soluble than their trans-analogs. Consistent with mucin's linear morphology, cis-glycopolymers were more potent binders of a bacterial virulence factor, cholera toxin. Our findings highlight the importance of the polymer backbone in mucin surrogate design and underscore the significance of the extended mucin backbone for inhibiting virulence.
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
10.1021/ACSCENTSCI.0C01569
