Spatial conformation of glycans and glycoproteins.

Ten years ago, we anticipated future results by building the Y-shaped molecular model of a biantennary glycan. Progressively, this structure has been refined and modified thanks to experimental data obtained by using physical methods: X-ray diffraction, electron spin resonance (EPR), nuclear magnetic resonance (NMR) including two-dimensional NMR and one-dimensional 1H-nuclear Overhauser effect (NOE) experiments, neutron scattering and hard-sphere exo-anomeric (HSEA) calculations. So, the concept evolved successively from the Y-, to the T-, the bird- and the "broken wing"-conformation, until the demonstration, that these conformers are interconvertible. The bird-conformation as well as the concept of the mobility of antennae are in a good agreement with the reactivity of lectins, including membrane lectins, by rendering accessible any specific sugar structure, and with the activity of glycosyltransferases by making reachable the substitutable hydroxyl groups even in the case of pentaantennary structures. Along this line, we know now that the tetraantennary glycans adopt an "umbrella conformation" in which the four antennae are disposed parallely to the protein surface and act as protective shields. So could be explained the resistance towards proteases and the weak antigenicity of numerous glycoproteins as well as the peculiar behaviour and resistance of metastatic cancerous cells since it has been recently demonstrated that membrane glycoproteins and fibronectin of this kind of cells are significantly enriched in tri- and tetraantennary glycans.