Curr Opin Chem Biol. 2026 Sep 2;94:102753. doi: 10.1016/j.cbpa.2026.102753. Online ahead of print.

ABSTRACT

Proteoglycans (PGs) are intricate macromolecules decorated with linear polysulfated glycosaminoglycans (GAGs) that play critical roles in orchestrating a wide range of physiological and pathological events. Advances in the utilization of recombinant enzymes and biosynthetic pathways have expedited the production of defined and homogeneous GAGs, helping overcome traditional barriers of chemical synthesis. Furthermore, the synthesis of GAG chains has been increasingly integrated with other critical structural elements, most notably the core proteins. Robust synthetic methodologies toward well-defined GAGs and entire PG structures are critical because there is a lack of comprehensive structure-function data that addresses the PG architecture as a unified glycoconjugate. The construction of homogeneous PG is a formidable and rapidly evolving frontier in chemical biology, and the latest developments in this arena are summarized in this review.

PMID:42685652 | DOI:10.1016/j.cbpa.2026.102753