Synthesis of 9-Substituted Sialic Acids as Probes for CD22-Ligand Interactions on B Cells

As a member of the sialic acid binding immunoglobulin-like lectins (siglecs) family, the B cell protein CD22 binds to NeuAc alpha 2-6Gal terminated glycans of glycoproteins on the same cell (in cis) and on adjacent cells (in trans). As a route to develop ligands with altered biological properties, sialic acid analogs with C-9 substitutions were efficiently synthesized from 9-azido-NeuAc, which was obtained in two steps in 65% overall yield from neuraminic acid. 9-Substituted sialic acid analogs were incorporated into cell surface glycoproteins of B cells via the normal cellular biosynthetic pathway, providing unique approaches for the study of CD22-ligand interaction, including in situ photoaffinity crossliking to cis ligands, and modulating the binding affinity with both cis and trans ligands in the cellular context.