What is the Sugar Code?

Abstract

A code is defined by the nature of the symbols, which are used to generate information-storing combinations (e. g. oligo-and polymers). Like nucleic acids and proteins, oligo-and polysaccharides are ubiquitous, and they are a biochemical platform for establishing molecular messages. Of note, the letters of the sugar code system (third alphabet of life) excel in coding capacity by making an unsurpassed versatility for isomer (code word) formation possible by variability in anomery and linkage position of the glycosidic bond, ring size and branching. The enzymatic machinery for glycan biosynthesis (writers) realizes this enormous potential for building a large vocabulary. It includes possibilities for dynamic editing/erasing as known from nucleic acids and proteins. Matching the glycome diversity, a large panel of sugar receptors (lectins) has developed based on more than a dozen folds. Lectins 'read' the glycan-encoded information. Hydrogen/coordination bonding and ionic pairing together with stacking and CÀ H/π-interactions as well as modes of spatial glycan presentation underlie the selectivity and specificity of glycan-lectin recognition. Modular design of lectins together with glycan display and the nature of the cognate glycoconjugate account for the large number of post-binding events. They give an entry to the glycan vocabulary its functional, often context-dependent meaning(s), hereby building the dictionary of the sugar code.

Combination of High-Resolution Multistage Ion Mobility and Tandem MS with High Energy of Activation to Resolve the Structure of Complex Chemoenzymatically Synthesized Glycans

“…The identification of precise glycosylation patterns creates a highly specific language, known as the glycocode. 2 In the living cell, the glycome (composed by cell surface glycans and secreted glycans) is the less conserved biomolecule of evolution. However, while featuring the largest informational diversity, it remains very far behind the genome, the transcriptome, the proteome, the metabolome, and the lipidome in terms of knowledge base.…”

“…As shown by Laine, the number of possible isomers calculated for reducing hexasaccharides composed only of d -hexoses, including linear and branched forms, is above 10 12 . The identification of precise glycosylation patterns creates a highly specific language, known as the glycocode . In the living cell, the glycome (composed by cell surface glycans and secreted glycans) is the less conserved biomolecule of evolution.…”

A pore-forming β-trefoil lectin with specificity for the tumor-related glycosphingolipid Gb3

“…Lectins are protein receptors that bind complex carbohydrates without modifying them, and therefore participating in the signaling function of the glycocode encoded in glycoconjugates such as glycolipids and glycoproteins at the cell surface 1,2 . Lectins participate in multiple biological processes, such as embryonic development, cell growth and immunomodulation, and are crucial for the interactions between microorganisms and host cells (pathogenicity, symbiosis).…”

Protein cysteine S-glycosylation: oxidative hydrolysis of protein S-glycosidic bonds in aqueous alkaline environments

“…According to the literature, protein S-glycosylation occurs in prokaryotic and eukaryotic cells. These modifications may be more widespread than evidenced by the current state of knowledge, and could even be seen as new structural elements of the sugar code system (Gabius et al 2021 ).…”