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Abstract
The view on the significance of the presence of glycans in glycoconjugates is undergoing a paradigmatic change. Initially mostly considered to be rather inert and passive, the concept of the sugar code identifies glycans as highly versatile platform to store information. Their chemical properties endow carbohydrates to form oligomers with unsurpassed structural variability. Owing to their capacity to engage in hydrogen (and coordination) bonding and C-H/π-interactions these “code words” can be “read” (in Latin, legere) by specific receptors. A distinct class of carbohydrate-binding proteins are the lectins. More than a dozen protein folds have developed carbohydrate-binding capacity in vertebrates. Taking galectins as an example, distinct expression patterns are traced. The availability of labeled endogenous lectins facilitates monitoring of tissue reactivity, extending the scope of lectin histochemistry beyond that which traditionally involved plant lectins. Presentation of glycan and its cognate lectin can be orchestrated, making a glycan-based effector pathway in growth control of tumor and activated T cells possible. In order to unravel the structural basis of lectin specificity for particular glycoconjugates mimetics of branched glycans and programmable models of cell surfaces are being developed by strategic combination of lectin research with synthetic and supramolecular chemistry.
Highlights
The view on the significance of the presence of glycans in glycoconjugates is undergoing a paradigmatic change
What sounds rather academic and complex can best be illustrated by looking at the research strategy and emerging results in the case of a distinct family, preferably with biomedical relevance. In view of their involvement in diverse processes such as cell adhesion, growth regulation, mediator release and migration as well as intracellular activities such as regulation of gene expression or apoptosis [31,41,51,52,78,79,80,81,82], galectins serve as such an instructive test study object
The intricacies of cell sociology depend on the presentation of a multitude of signals with distinct information content on the cell surface
Summary
Biochemical coding can be likened to a language. Oligo- and polymers are the biochemical equivalents of “words” and “sentences”. Built from the alphabets of nucleotides and amino acids, the information content of nucleic acids and proteins is determined by the sequence (order of “letters”) In both cases, the “letters” are connected in the same way (type of linkage and points of attachment; Figure 1a,b). In the concept of the sugar code these intimately controlled core substitutions should have their own importance Both the bisecting GlcNAc moiety and the core fucose unit are not inert additions to the N-glycan but act on its conformational behavior like molecular switches. The complete definition of any di- or oligosaccharide in structural terms requires the determination of the linkage points and the type of anomery Addressing these issues makes carbohydrate sequencing (and synthesis) much more demanding than respective work on nucleic acids and proteins, explaining the origin of the often used term “complex carbohydrate”.
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