We have tentatively identified a new group of complex-type N-linked oligosaccharides that contain covalently bound amino acids on their antennae. A carboxylate-specific monoclonal antibody shows that these species are enriched in endothelial cells, embryonic neurons, cancer cells, and on the Receptor for Advanced Glycation End products (RAGE). The carboxylated glycans directly bind to three proteins: amphoterin, annexin-I and S100A8/A9, which have been linked in various ways to inflammation, septic shock, and tumor growth/metastasis. Significantly, we also found that the novel sugar chains mediate endothelium/leukocyte binding, intraperitoneal inflammation, neurite outgrowth, and binding of purified RAGE to amphoterin. Unfortunately, we do not know the precise structure(s) of the carboxylated oligosaccharides. Therefore, our aim is: To establish the structure of these novel and physiologically important glycans. Establishing these structures is critical for understanding the molecular basis of their involvement in the pathophysiology described above and for designing therapeutic strategies. The impact of solving these structures could be quite substantial. However, in the past, we have had difficulty establishing this structure, and therein lies the risk in this project and why it responds to PA-97-049.
| Srikrishna, Geetha; Brive, Lena; Freeze, Hudson H (2005) Novel carboxylated N-glycans contain oligosaccharide-linked glutamic acid. Biochem Biophys Res Commun 332:1020-7 |
