Synthesis of a multivalent display of a CD22-binding trisaccharide

Multivalent interactions have been implicated in the binding of B-cell surface glycoprotein CD22 to its physiological ligands. Because CD22 can influence B-cell antigen receptor (BCR) signaling, multivalent ligands that cluster CD22 may influence B-cell responses. Here, we report an efficient synthesis of a fluorophore-labeled multivalent display of a CD22-binding trisaccharide, Neu5Acalpha2,6Galbeta1,4Glc, using the ring-opening metathesis polymerization (ROMP). Our synthetic strategy involves the modification of an N-hydroxysuccinimide (NHS) ester-substituted polymer generated by ROMP with the aminopropyl glycoside of the trisaccharide. The conjugation efficiency for the coupling is high; when 0.3 equiv of the trisaccharide derivative were used relative to NHS ester groups, the mole fraction (chi) of trisaccharide ligand incorporated onto the backbone was 0.3. A fluorescein-labeled version of the multivalent ligand binds to cells expressing CD22.