Chemoenzymatic synthesis of dendritic sialyl Lewis x

Abstract

Traditional structure activity relationship studies (SAR) have led to the development of numerous sialyl Lewis x analogs in the search for potential antiinflammatory agents. However, these methods do not take into account cluster or multivalent effects. Reported herein is the chemoenzymatic synthesis of di-, tetra-, and octa-valent sLe x ligands scaffolded on dendrimers. Hypervalent l-lysine cores with covalently attached 2-acetamido-2-deoxy- d-glucose ( N-acetylglucosamine, GlcNAc) residues were chemically prepared and enzymatically transformed into sLe x-containing dendrimers so that multivalency, and its role in selectin-sLe x interactions may be evaluated. This work constitutes another successful enzymatic synthesis of sLe x and represents the first example of GlcNAc elongation on a synthetic dendrimer scaffold. These sLe x dendrimers are currently being investigated as selectin antagonists.