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Published June 2024 | Published
Journal Article

Recent advances in the synthesis of extensive libraries of heparan sulfate oligosaccharides for structure–activity relationship studies

Abstract

Heparan sulfate (HS) is a linear, sulfated and highly negatively-charged polysaccharide that plays important roles in many biological events. As a member of the glycosaminoglycan (GAG) family, HS is commonly found on mammalian cell surfaces and within the extracellular matrix. The structural complexities of natural HS polysaccharides have hampered the comprehension of their biological functions and structure–activity relationships (SARs). Although the sulfation patterns and backbone structures of HS can be major determinants of their biological activities, obtaining significant amounts of pure HS from natural sources for comprehensive SAR studies is challenging. Chemical and enzyme-based synthesis can aid in the production of structurally well-defined HS oligosaccharides. In this review, we discuss recent innovations enabling the syntheses of large libraries of HS and how these libraries can provide insights into the structural preferences of various HS binding proteins.

Copyright and License

© 2024 Elsevier.

Acknowledgement

This word was supported by the National Institute of General Medical Sciences, NIH (R01GM072667, U01GM116262, R44GM134738, and U01GM112648) and Michigan State University.

Contributions

Sherif Ramadan: Conceptualization (supporting); Writing – original draft (leading); Writing – review and editing (supporting); Morgan Mayieka: Conceptualization (supporting); Writing – original draft (supporting); Writing – review and editing (supporting); Nicola L. B. Pohl: Conceptualization (supporting); Writing – review and editing (supporting); Jian Liu: Conceptualization (supporting); Writing – review and editing (supporting); Linda C. Hsieh-Wilson: Conceptualization (supporting); Writing – review and editing (supporting); Xuefei Huang: Conceptualization (leading); Writing – original draft (supporting); Writing – review and editing (leading).

Data Availability

No data was used for the research described in the article.

Conflict of Interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xuefei Huang reports financial support was provided by National Institutes of Health. Jian Liu reports financial support was provided by National Institutes of Health. Nicola Pohl reports financial support was provided by National Institutes of Health. Linda Hsieh-wilson reports financial support was provided by National Institutes of Health. Jian Liu reports a relationship with Glycan Therapeutics, LLC that includes: equity or stocks. Xuefei Huang reports a relationship with Glycan Therapeutics, LLC that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional Information

This review comes from a themed issue on Carbohydrate Synthesis (2024)Edited by Yang You and Biao Yu.

Additional details

Created:
May 30, 2024
Modified:
May 30, 2024