McBerney, R, Dolan, JP, Cawood, EE, Webb, ME and Turnbull, WB (2022) Bioorthogonal, Bifunctional Linker for Engineering Synthetic Glycoproteins. JACS Au. ISSN 2691-3704

[thumbnail of jacsau.2c00312.pdf]
jacsau.2c00312.pdf - Published Version

Download (3MB) | Preview


Post-translational glycosylation of proteins results in complex mixtures of heterogeneous protein glycoforms. Glycoproteins have many potential applications from fundamental studies of glycobiology to potential therapeutics, but generating homogeneous recombinant glycoproteins using chemical or chemoenzymatic reactions to mimic natural glycoproteins or creating homogeneous synthetic neoglycoproteins is a challenging synthetic task. In this work, we use a site-specific bioorthogonal approach to produce synthetic homogeneous glycoproteins. We develop a bifunctional, bioorthogonal linker that combines oxime ligation and strain-promoted azide–alkyne cycloaddition chemistry to functionalize reducing sugars and glycan derivatives for attachment to proteins. We demonstrate the utility of this minimal length linker by producing neoglycoprotein inhibitors of cholera toxin in which derivatives of the disaccharide lactose and GM1os pentasaccharide are attached to a nonbinding variant of the cholera toxin B-subunit that acts as a size- and valency-matched multivalent scaffold. The resulting neoglycoproteins decorated with GM1 ligands inhibit cholera toxin B-subunit adhesion with a picomolar IC50.

Item Type: Article
Additional Information: The final version of this article and all relevant information related to it, including copyrights, can be found on the publisher website.
Subjects: Q Science > QD Chemistry
Q Science > QD Chemistry > QD415 Biochemistry
Depositing User: Symplectic
Date Deposited: 28 Sep 2022 12:04
Last Modified: 28 Sep 2022 12:04

Actions (login required)

View Item
View Item