Synthesis of Cyclic Glycopolymers Presenting Sialyllactose Derivatives Toward Siglec-Mediated Signal Suppression.

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of membrane proteins that bind sialic acids, most of which possess cytoplasmic immunoreceptor tyrosine-based inhibitory motifs. Glycoligands capable of modulating Siglec-mediated responses therefore have potential as therapeutic agents for immune-related diseases. Herein, we synthesized linear and cyclic glycopolymers that multivalently present sialic acid ligands targeting Siglec-E, which is highly expressed on murine macrophages, and evaluated the effect of polymer topology on Siglec-mediated signal suppression. Although no significant difference was observed between the two polymer architectures, the glycopolymers suppressed NF-κB signaling more effectively than the monomeric sialic acid ligand.