Abstract
Proteoglycans (PGs) are composed of a protein moiety and a complex glycosaminoglycan (GAG) polysaccharide moiety. GAG chains are responsible for various biological activities. GAG chains are covalently attached to serine residues of the core protein. The first step in PG biosynthesis is xylosylation of certain serine residues of the core protein. A specific linker tetrasaccharide is then assembled and serves as an acceptor for elongation of GAG chains. If the production of endogenous GAG chains is selectively inhibited, one could determine the role of these endogenous molecules in physiological and developmental functions in a spatiotemporal manner. Biosynthesis of PGs is often blocked with the aid of nonspecific agents such as chlorate, a bleaching agent, and brefeldin A, a fungal metabolite, to elucidate the biological roles of GAG chains. Unfortunately, these agents are highly lethal to model organisms. Xylosides are known to prime GAG chains. Therefore, we hypothesized that modified xylose analogs may able to inhibit the biosynthesis of PGs. To test this, we synthesized a library of novel 4-deoxy-4-fluoroxylosides with various aglycones using click chemistry and examined each for its ability to inhibit heparan sulfate and chondroitin sulfate using Chinese hamster ovary cells as a model cellular system.
Highlights
Proteoglycans are composed of a core protein and one or more glycosaminoglycan (GAG)4 side chains such as chondroitin sulfate (CS) and heparan sulfate (HS)
GAG chains isolated from analog-treated hepatocytes were shown to be smaller in size than those isolated from control cells
As an approach to perturb GAG biosynthesis, we propose that 4-deoxy-4-fluoroxylosides cannot prime GAG chains as they do not have an acceptor hydroxyl group at C-4 for subsequent sugar attachment and elongation
Summary
Proteoglycans are composed of a core protein and one or more glycosaminoglycan (GAG)4 side chains such as chondroitin sulfate (CS) and heparan sulfate (HS). These modified xylosides could affect galactosyltransferase-1, an enzyme involved in assembly of the linkage region, and thereby inhibit PG biosynthesis.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
