Keynote Lecture
Orchestrating the Interplay between Lectins and Carbohydrates

All cells are covered with a molecular layer of glycoconjugates with particular complexity, dimension and biological significance. This extracellular compartment is called a cell’s glycocalyx. Molecular recognition of glycocalyx constituents and their interaction with specialized proteins, the lectins, are fundamental to cell biology. Hence, the molecular regime of glycoconjugates characterizes an individual organism both in health and disease states.

In order to gain a detailed understanding of how carbohydrate-lectin interactions are orchestrated within the supramolecular environment of the glycocalyx, my group has utilized synthetic derivatives of natural glycoconjugates as well as so-called glycoarrays.¹ This has allowed us to mimic specific characteristics of the glycocalyx and to address particular questions and hypotheses about the principles underlying carbohydrate recognition. As a relevant biological system for the investigation of cell-cell interactions, we are exploring carbohydrate-specific adhesion of bacterial cells to surfaces.² In bacterial adhesion, we have tested carbohydrate specificity,³ multivalency effects,⁴ and more recently, orientational and steric control of cell adhesion,⁵ involving photoswitchable molecular tools.⁶ The talk will detail our recent approaches in orchestration and organization of carbohydrates recognition.

References

1. A ‘dual click’ strategy for the fabrication of bioselective, glycosylated self-assembled monolayers as glycocalyx models. C. Grabosch, M. Kind, Y. Gies, F. Schweighöfer, A. Terfort, Th. K. Lindhorst. Org. Biomol. Chem. 2013, 11, 4006-4015.
2. The Bacterial Lectin FimH, a Target for Drug Discovery ― Carbohydrate Inhibitors of Type 1 Fimbriae-Mediated Bacterial Adhesion. Review. M. Hartmann, Th. K. Lindhorst. Eur. J. Org. Chem. 2011, 3583-3609.
3. Ligands for FimH. Th. K. Lindhorst in: Synthesis and Biological Applications of Glycoconjugates, O. Renaudet, N. Spinelli (Eds.), Bentham eBooks, 2011, pp 12-35.
4. Multivalent glycoconjugates as anti-pathogenic agents. A. Bernardi et al. Chem. Soc. Rev. 2013, 42, 4709-4727.
5. Switching of bacterial adhesion to a glycosylated surface by reversible reorientation of the carbohydrate ligand. T. Weber, V. Chandrasekaran, I. Stamer, M. B. Thygesen, A. Terfort, Th. K. Lindhorst. Angew. Chem. Int. Ed. 2014, 53, 14583-14586.
6. Switching first contact: photocontrol of E. coli adhesion to human cells. L. Möckl, A. Müller, C. Bräuchle, Th. K. Lindhorst. Chem. Commun. 2016, 52, 1254-1257.