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

Sherif Ramadan; Morgan Mayieka; Nicola L B Pohl; Jian Liu; Linda C Hsieh-Wilson; Xuefei Huang

doi:10.1016/j.cbpa.2024.102455

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

Curr Opin Chem Biol. 2024 Apr 17:80:102455. doi: 10.1016/j.cbpa.2024.102455. Online ahead of print.

Authors

Sherif Ramadan¹, Morgan Mayieka², Nicola L B Pohl³, Jian Liu⁴, Linda C Hsieh-Wilson⁵, Xuefei Huang⁶

Affiliations

¹ Department of Chemistry, Michigan State University, 578 S. Shaw Lane, East Lansing, MI 48824, USA; Chemistry Department, Faculty of Science, Benha University, Benha, Qaliobiya 13518, Egypt.
² Department of Chemistry, Michigan State University, 578 S. Shaw Lane, East Lansing, MI 48824, USA.
³ Department of Chemistry, Indiana University, 212 S. Hawthorne Drive, Bloomington, IN 47405, USA.
⁴ Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
⁵ Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
⁶ Department of Chemistry, Michigan State University, 578 S. Shaw Lane, East Lansing, MI 48824, USA; Institute for Quantitative Health Science and Engineering, East Lansing, MI 48824, USA; Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA. Electronic address: huangxu2@msu.edu.

PMID: 38636446
DOI: 10.1016/j.cbpa.2024.102455

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.

Keywords: Automation; Heparan sulfate; Library synthesis; Solid phase; Structure activity relationship.

Publication types

Review