Structural advances of Siglecs: insight into synthetic glycan ligands for immunomodulation

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are transmembrane proteins of the immunoglobulin (Ig) superfamily predominantly expressed on the cells of our immune system. Siglecs recognize sialic acid via their terminal V-set domain. In mammals, sialic acid-terminated glycolipids and glycoproteins are the ligands of Siglecs, and the monomeric affinity of Siglecs for their sialic acid-containing ligands is weak. Significant efforts have been devoted toward the development of chemically modified sialoside ligands to target Siglecs with higher affinity and selectivity. In this review we discuss natural and synthetic sialoside ligands for each human Siglec, emphasizing the ligand binding determinants uncovered from recent advances in protein structural information. Potential therapeutic applications of these ligands are also discussed.