Dendrimer-like PEO Glycopolymers Exhibit Anti-Inflammatory Properties

摘要

Selectin-induced leukocyte rolling on endothelial surfaces is an essential step in mediating events leading to inflammatory and cell-mediated immune responses.Characteristically,the adhesion cascade is facilitated by the interaction of selectins with O-glycosylated protein ligands that present sulfated derivatives of the tetrasaccharide sialyl Lewis x (Neu5Acalpha3Galbeta4(Fuca3)GlcNAc-,sLe~x).Significant effort has been directed toward generating sLe~x mimetics in the form of small molecules,polymers,liposomes,and protein conjugates,as competitive inhibitors of selectin-mediated binding events.However,relatively weak affinity,susceptibility to hydrolytic cleavage,potential antigenicity,and short circulating half-life,in addition to the absence of a convenient synthetic route are acknowledged limitations of sLe~x-derivatized bioconjugates.Thus,motivation exists to develop simpler therapeutic oligo-saccharide analogues as selectin-binding antagonists,which exhibit multiple and cooperative receptor binding properties.