Chemical Strategies to Custom-Modify α(1→3)-Fucosylated Glycan Motifs of the Human Glycocalyx.

In mammals, every cell is covered by a sugar coat called the "glycocalyx", a meshwork created by sugar modifications of cell surface proteins and lipids. Essentially all cell membrane proteins and lipids contain oligosaccharide clusters known as "glycan motifs" that confer distinct functional properties on these respective glycoproteins or glycolipids. These motifs are generated by glycosyltransferases that assemble the component monosaccharides in a stereospecific and regiospecific fashion. Glycocalyx motifs bearing l-fucose in α(1→3) linkage to -acetyl-glucosamine are found on a highly restricted subset of membrane glycoproteins and glycolipids, and changes in α(1→3)-fucosylation levels impact a wide range of physiologic and pathologic processes. Within this biological framework, we herein review the pivotal role of α(1→3)-fucosylation in cell biology and then comprehensively review the evolving chemical strategies to custom-modify α(1→3)-fucosylation of the glycocalyx to achieve highly specific control of human cell surface fucosylated glycan motifs. These efforts serve as a prime example of how the fine control of cell surface fucosylation can enable the generation of glycan-based precision therapeutics, driving forward the field of "translational glycobiology".