Sugars in Nature

Carbohydrates are the most abundant biological molecules, and fill numerous roles in all living organisms including energy storage and transport (e.g. starch, glycogen), support structures (e.g. cellulose, chitin), and major roles in the functioning of the immune system, fertilization, pathogenesis, blood clotting, differentiation and development. Even the fundamental ‘codes’ of life (DNA and RNA) are carbohydrate-based polymers. Given the incredible variation of carbohydrates (see Sugar Fundamentals), nature often relies upon carbohydrates as "recognition tools" wherein the carbohydrate structures act as signal or recognition markers to mediate cell-to-cell recognition, cell-to-cell adhesion and molecular targeting. Changes in expression of carbohydrate patterns are also often observed in the context of inflammatory diseases, pathogenic infections and even progression to malignancy. In general, carbohydrates attached to organic molecules dramatically change the molecule’s physical, chemical and biological properties. Within the context of such bioactive glycoconjugates, the attached sugars notably impact the biosynthesis, stability, distribution, mechanism, specificity and turnover of these molecules in living organisms (see also Sugars in Medicine). Given the overwhelming importance of carbohydrates in health and disease, robust glycosylation platforms such the Centrose approach are anticipated to greatly advance the future of the biotechnology and pharmaceutical industries.

Glycoconjugates are molecules with sugars attached. The attached sugars can have dramatic effects on the biosynthesis, stability, localization, trafficking, action, and turnover of these molecules in intact organisms. For this reason alone, glycobiology and carbohydrate chemistry have become of increasing importance in modern biotechnology. In addition, many important biological interactions and functions mediated by glycans (see Glycans below) are potentially amenable to manipulation in vivo. Furthermore, several human disease states are characterized by changes in glycan biosynthesis that can be of diagnostic and/or therapeutic significance.

In naturally occurring sugar conjugates, the portion of the molecule comprising the sugar can vary greatly, from being very minor in amount to being the dominant component. Indeed, it is striking that sugar chains make up a substantial portion of the mass of most glycoconjugates. For this reason, the surfaces of most types of cells are covered with a dense coating of sugars. Newly synthesized proteins originating from the ER are modified with sugar chains. Well-characterized pathways for the biosynthesis of different classes of sugars occur within the ER-Golgi pathway. Most glycosylation reactions utilize activated forms of monosaccharides that are catalyzed by enzymes called glycosyltransferases. Much effort has gone into understanding the mechanisms of glycosylation and it is clear that a variety of factors determine the final outcome of glycosylation reactions. Like all components of living cells, glycans are constantly being created and degraded. Degradation is mediated by enzymes that cleave sugar chains either at the outer (nonreducing) terminal end (exoglycosidases) or internally (endoglycosidases). Some outer units can also be removed and then reattached without degradation of the underlying chain. The final complete degradation of most glycans is generally carried out by a series of glycosidases. Unlike oligonucleotides and proteins, glycan chains are rarely expressed in a linear, unbranched fashion, and even when they are, such chains are often subject to various modifications. Thus, the complete sequencing of oligosaccharides is difficult to accomplish. A variety of specific genetic defects have been defined in mutant variants that express specific defects in glycan biosynthesis. These mutants have been of great value in elucidating the details of glycan biosynthetic pathways. Centrose plans to establish future programs aimed at applying its technologies to the production and modification of therapeutically useful glycans.

Glycans are composed of multiple linked sugars and are essential structural components of living cells and a source of energy for animals (http://en.wikipedia.org/wiki/Glycans). The diverse biological functions attributed to glycans can be grouped into two general classes: (1) structural and modulator functions involving the glycans or glycan modulation of molecules to which they are attached and (2) specific recognition of glycans by lectins (carbohydrate-binding proteins). Glycans are widely distributed in nature and recently their study has become one of the more rapidly growing fields in the biomedical sciences, with relevance to basic research, biomedicine, and biotechnology. Indeed, several biotechnology, pharmaceutical, and laboratory supply companies have invested heavily in the area. The field ranges from the chemistry of carbohydrates and the enzymology of glycan-modifying proteins to the functions of glycans in complex biological systems, and their manipulation by a variety of techniques. Research in glycobiology requires a foundation not only in the nomenclature, biosynthesis, structure, chemical synthesis, and functions of complex glycans, but also in the general disciplines of molecular genetics, cellular biology, physiology, and protein chemistry.

CarboConnect and Sugar Pirating provide the needed methodologies for the study and exploitation of many aspects of glycobiology.