Recent advances in the chemical synthesis of Glycosaminoglycans.

Abstract

Glycosaminoglycans (GAGs) are complex carbohydrates ubiquitously expressed on cell surfaces and within the extracellular matrix, where they regulate essential biological processes through sequence- and sulfation-dependent interactions. Major GAG classes, including heparan sulfate (HS), chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS), and hyaluronic acid (HA), exhibit diverse sulfation patterns that encode specific molecular recognition events. Deciphering their structure-activity relationships has been hindered by intrinsic heterogeneity and limited access to well-defined materials. This review focuses on the recent advances in the chemical synthesis of GAGs, highlighting strategies that enable precise control over GAG structure and sulfation patterns. Recent innovations in protecting group design, stereoselective glycosylation, and automated assembly have significantly improved synthetic efficiency, facilitating the construction of increasingly complex and biologically relevant structures and advancing the rational design of GAG-based tools and therapeutics.