Metabolic Oligosaccharide Engineering: Implications for Selectin-Mediated Adhesion and Leukocyte Extravasation

Abstract

Metabolic oligosaccharide engineering is an emerging technology wherein non-natural monosaccharide analogs are exogenously supplied to living cells and are biosynthetically incorporated into cell surface glycans. A recently reported application of this methodology employs fluorinated analogs of ManNAc, GlcNAc, and GalNAc to modulate selectin-mediated adhesion associated with leukocyte extravasation and cancer cell metastasis. This monograph outlines possible mechanisms underlying the altered adhesion observed in analog-treated cells; these range from the most straightforward explanation (e.g., structural changes to the selectin ligands ablate interaction with their receptors) to the alternative mechanism where the analogs inhibit or otherwise perturb ligand production to more indirect mechanisms (e.g., changes to the biophysical properties of the selectin binding partner, the nanoenviroment of the binding partners, or the entire cell surface).