Tales from the Sweet Side of Life : Structure and dynamics of carbohydrate-based systems

The field of glycomics has experienced significant developments in the last few decades, revealing a profound and elaborate language behind the intrinsic complexity of the glycans structures. This ‘sugar code’ is at the basis of intercellular interaction and recognition. For this language to be understood, its chemical basis must be unveiled. Two main techniques have played a significant role in this area: NMR spectroscopy and molecular dynamics simulations. In this thesis, via the combined approach of these two techniques, we get an insight of three different aspects of carbohydrate analysis, such as structure elucidation, conformation and dynamics, and interaction mechanisms with specialized proteins. The thesis is divided in three parts. The first part will uncover the biological role of streptococcal bacteria cell wall polysaccharides. Using a variety of different biological, biochemical, and spectroscopic tools, we describe their biosynthesis, structures – including newly discovered substituents – and biological significance. These rhamnose containing polysaccharides are the basis for the bacterial first-line protection against external offense and, at the same time, a Trojan horse for us to eradicate as yet persistent streptococcal pathogens-related diseases. The second part focuses on the conformational analysis of small mannose- and glucose-derivatives using NMR spectroscopy and molecular dynamics simulations. Particularly, the effect of methyl substitution in glucose oligosaccharides is investigated from a structural and thermodynamic point of view. Additionally, polarizable force fields were tested in the conformational analysis of different naturally occurring α-linked mannose disaccharide and compared to previously developed force fields. In the last part, using the same set of techniques, we elucidate the binding mode of small mannose oligosaccharides to the cyanobacterium protein Cyanovirin-N. This interaction is the basis of the virucidal activity of the protein against HIV infections