Glycobiology & Glycochemistry

Glycobiology is the study of the structure, biosynthesis and biology of saccharides that are widely distributed in nature. Sugars or saccharides are essential components of all living things and aspects of the various roles they play in biology and are researched in various medical, biochemical and biotechnological fields. The study of glycan structures is also complicated by the lack of a direct template for their biosynthesis, contrary to the case with proteins where their amino acid sequence is determined by their corresponding gene.

Mass spectrometry (MS) - based proteomics allows the sensitive and accurate quantification of almost complete proteomes of complex biological fluids and tissues. At the moment, however, the routinely usage of MS-based proteomics is prevented and complicated by the very complex work flow comprising sample preparation, chromatography, MS measurement followed by data processing and evaluation. The new technologies, products and assays developed by Precision Proteomics could help enabling and establishing mass spectrometry (MS) - based proteomics in academic and pharmaceutical research as well as in clinical diagnostics.

Glycans are components of many bio-therapeutic agents, ranging from natural products to molecules based on rational design to recombinant glycoproteins. The glycan components of these agents can be important determinants of their biological activity and therapeutic efficacy. Biochemistry and Glycobiology involves a multidisciplinary study of carbohydrate-binding proteins (lectins), glycolipids  and some other plant proteins that are capable of interacting with endogenous or foreign (macro) molecules.

Glycobiology along with the field of proteomics, particularly the application of mass spectrometry analysis to protein samples, is well-established and growing rapidly. Proteomics studies along with glycans generate large volumes of raw experimental data and inferred biological results. To facilitate the dissemination of these data, centralized data repositories have been developed that make the data and results accessible to proteomics researchers and biologists alike. Experimental analysis of proteomics data repositories focuses exclusively on freely-available, centralized data resources that disseminate or store experimental mass spectrometry data and results.

Glycobiology and Glycochemistry are the two main intertwined areas of Glycosciences, dealing with various aspects of glycans, including carbohydrate structure, biochemistry, biological functions and applications. This is necessary in order to sustain and advance the identification of key glycobiological aspects and the application of glycans and glyco-engineering strategies in the design of novel therapies to improve human health. Drug targeting is important for our understanding of human health and disease, and for the development of new therapeutic strategies.

Glycomics the scientific attempt to characterize and study carbohydrates, is a rapidly emerging branch of science, for which informatics is just beginning. Glycomics requires sophisticated algorithmic approaches. Several algorithms and models have been developed for glycobiology research in the past several years. The development and use of informatics tools and databases for glycobiology and glycomics research has increased considerably in recent years. However, the general development in this field can still be considered as being in its infancy when compared to the genomics and proteomics areas. In terms of bioinformatics in glycobiology, there are several paths of research that are currently in progress. The development of algorithms and software tools for interpretation of glycans to reliably support the characterization of glycan structures for high-throughput applications is the most immediate demand of the glycomics community.

Glycans can mediate a wide variety of biological roles by virtue of their mass, shape, charge, or other physical properties. However, many of their more specific biological roles are mediated via recognition by GBPs. Nature appears to have taken full advantage of the vast diversity of glycans expressed in organisms by evolving protein modules to recognize discrete glycans that mediate specific physiological or pathological processes. The natural ligands for most lectins are typically complex glycoconjugates that carry clustered arrays of the cognate carbohydrate or unique glycan structures, thus cooperating with clustered lectin-binding sites to generate high-avidity binding, which is further enhanced by mass transport effects (high local concentrations of ligands).

Glycans quickly became overshadowed as DNA- and protein-focused treatments became readily accessible. The recent development of new tools and techniques to study and produce structurally defined carbohydrates has spurred renewed interest in the therapeutic applications of glycans. Glycan Analysis review focuses on advances within the past decade that are bringing glycan-based treatments back to the forefront of medicine and the technologies that are driving these efforts. These include the use of glycans themselves as therapeutic molecules as well as engineering protein and cell surface glycans to suit clinical applications to that of databases providing glycoenzyme data. Glycoconjugates offer a rich and promising frontier for developments in the academic, biopharmaceutical, and medical fields.

Glycomics is a discipline in genetics that applies recombinant DNA, DNA sequencing methods and bioinformatics to sequence, assemble and analyze the function and structure of glycans along with the genomes. Metabolomics is a relatively young branch of omics science concerned with the systematic study of the chemical products or metabolites that cells and organisms generate. Indeed, most human metabolomic studies published today, even those exploiting the latest and most sensitive LC-MS/MS technologies, typically succeed in identifying or characterizing fewer than 100 compounds. This includes the human cerebrospinal fluid metabolome the human saliva metabolome and the human serum metabolome. 

Various approaches have taken to understand the biological roles of glycans which include the prevention of initial glycosylation, prevention of glycan chain elongation, alteration of glycan processing, enzymatic or chemical glycosylation of completed chains, genetic elimination of glycosylation sites, and the study of naturally occurring genetic variants and mutants in glycosylation. Glycosylation mainly refers in particular to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules. This enzymatic process produces one of the fundamental biopolymers found in cells (along with DNA, RNA, and proteins).

Glycans are saccharides that can be attached to a wide variety of biological molecules through an enzymatic process called glycosylation to augment their function. One of the four fundamental building blocks of life, proteins, carbohydrates (glycans), lipids and nucleic acids, glycans have received the least attention from researchers. Glycans are the predominant molecule on the cell surface and serve as the first point of contact between a cell and other cells, the extracellular matrix and pathogens. The heightened evolutionary pressure of being at the front lines of cellular collaboration and conflict most likely led to the diversification of glycans. Glyco-epitope diversity enhances the role of glycans in the group of debilitating and life-shortening disorders known as congenital muscular dystrophy, or CMD.

Glycobiology and Structural biology seeks to provide a complete and coherent picture of biological phenomena with glycans at the molecular and atomic level. The goals of structural biology include developing a comprehensive understanding of the molecular shapes and forms embraced by biological macromolecules and extending this knowledge to understand how different molecular architectures are used to perform the chemical reactions that are central to life. Most recent topics related to structural biology are: Structural Biochemistry, Structure and Function Determination, Glycolipids, Hybrid Approaches for Structure Prediction, Structural Biology in Cancer Research, Computational Approaches in Structural Biology, Structural Biology Databases

Carbohydrates were prominent in the early history of immunology in defining the identity of antigens recognized by antibodies. Numerous carbohydrate-binding proteins, or lectins, have been identified on the surfaces of immune cells. Interactions of lectins with glycans usually require several monosaccharide moieties presented in the correct conformation for high-affinity binding. Modification of proteins and lipids by glycosylation is a highly regulated process resulting in a diverse repertoire of glycan structures.

The human gut hosts trillions of bacteria that directly influence human health. The majority of gut microbiota play an important role in nutrition by metabolizing host-indigestible complex glycans into short-chain fatty acids. Growth of the mesh-like peptidoglycan (PG) sacculus located between the bacterial inner and outer membranes (OM) is tightly regulated to ensure cellular integrity, maintain cell shape, and orchestrate division. Asparagine (N)-linked protein glycosylation is a ubiquitous co- and post-translational modification which can alter the biological function of proteins and consequently affects the development, growth, and physiology of organisms. In mammals, complex N-glycans are involved in different cellular processes including molecular recognition and signalling events