High affinity sialoside ligands of myelin associated glycoprotein.

ABSTRACT: Myelin associated glycoprotein (Siglec-4) is a myelin adhesion receptor, that is, well established for its role as an inhibitor of axonal outgrowth in nerve injury, mediated by binding to sialic acid containing ligands on the axonal membrane. Because disruption of myelin-ligand interactions promotes axon outgrowth, we have sought to develop potent ligand based inhibitors using natural ligands as scaffolds. Although natural ligands of MAG are glycolipids terminating in the sequence NeuAcα2-3Galβ1-3(±NeuAcα2-6)GalNAcβ-R, we previously established that synthetic O-linked glycoprotein glycans with the same sequence α-linked to Thr exhibited ∼1000-fold increased affinity (∼1μM). Attempts to increase potency by introducing a benzoylamide substituent at C-9 of the α2-3 sialic acid afforded only a

SUBMITTER: Zeng Y 

PROVIDER: S-EPMC3156379 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature