Carbohydrate sulfation as a critical modulator of siglec-sialoglycan interactions
Jaesoo Jung, Edward N. Schmidt, Matthew S. Macauley
Abstract
Siglecs are sialic acid-binding immunomodulatory receptors that regulate immune homeostasis. Abnormal alterations in sialic acid-containing glycans (sialoglycans) on tissues or cells are key drivers of various diseases, including cancer, neurodegenerative disorders, allergies, and autoimmune diseases. Consequently, the role of Siglecs as immune checkpoints has gained increasing attention. To better understand Siglec biology, comprehensive approaches have been employed to elucidate Siglec ligands, including chemical synthesis for glycan microarrays and genetic manipulation of glycosyltransferases for understanding their biosynthesis process. These efforts have revealed that carbohydrate sulfation, catalyzed by carbohydrate sulfotransferases (CHSTs), fine-tunes Siglec-sialoglycan interactions by enhancing binding affinities. This review summarizes the latest insights into sulfated sialoglycan ligands for individual Siglecs.