Review

Authors: Navdeep S Chandel

Topics: Adenosine Triphosphate; Animals; Carbohydrate Metabolism; Carbohydrates; Disaccharides; Fructose; Gluconeogenesis; Glucose; Glycogen; Glycolysis; Homeostasis; Humans; Insulin; Monosaccharides

PubMed: 33397651
DOI: 10.1101/cshperspect.a040568

Authors: Elodie Drula, Marie-Line Garron, Suzan Dogan...

Thirty years have elapsed since the emergence of the classification of carbohydrate-active enzymes in sequence-based families that became the CAZy database over 20 years ago, freely available for browsing and download at www.cazy.org. In the era of large scale sequencing and high-throughput Biology, it is important to examine the position of this specialist database that is deeply rooted in human curation. The three primary tasks of the CAZy curators are (i) to maintain and update the family classification of this class of enzymes, (ii) to classify sequences newly released by GenBank and the Protein Data Bank and (iii) to capture and present functional information for each family. The CAZy website is updated once a month. Here we briefly summarize the increase in novel families and the annotations conducted during the last 8 years. We present several important changes that facilitate taxonomic navigation, and allow to download the entirety of the annotations. Most importantly we highlight the considerable amount of work that accompanies the analysis and report of biochemical data from the literature.

Topics: Carbohydrates; Databases, Nucleic Acid; Databases, Protein; Enzyme Activation; Enzymes; Humans

PubMed: 34850161
DOI: 10.1093/nar/gkab1045

Review

Authors: Pilar Garcia-Vello, Immacolata Speciale, Fabrizio Chiodo...

Carbohydrate adjuvants are safe and biocompatible compounds usable as sustained delivery systems and stimulants of ongoing humoral and cellular immune responses, being especially suitable for the development of vaccines against intracellular pathogens where alum is useless. The development of new adjuvants is difficult and expensive, however, in the last two years, seven new carbohydrate-based adjuvants have been patented, also there are twelve ongoing clinical trials of vaccines that contain carbohydrate-based adjuvants, as well as numerous publications on their mechanism of action and safety. More research is necessary to improve the existent adjuvants and develop innovative ones.

Topics: Adjuvants, Immunologic; Animals; Carbohydrates; Clinical Trials as Topic; Drug Development; Drug Evaluation, Preclinical; Humans; Immunity, Cellular; Immunity, Humoral; Models, Animal; Vaccination

PubMed: 33388128
DOI: 10.1016/j.ddtec.2020.09.005

Authors: Stefano Benini

Carbohydrate-active enzymes are responsible for both the biosynthesis and breakdown of carbohydrates and glycoconjugates [...].

Topics: Bacteria; Carbohydrates; Fungi; Glycoconjugates; Glycoside Hydrolases; Glycosyltransferases

PubMed: 32326403
DOI: 10.3390/ijms21082727

Review

Authors: Katharina Kappler, Thierry Hennet

Carbohydrate-specific antibodies are widespread among all classes of immunoglobulins. Despite their broad occurrence, little is known about their formation and biological significance. Carbohydrate-specific antibodies are often classified as natural antibodies under the assumption that they arise without prior exposure to exogenous antigens. On the other hand, various carbohydrate-specific antibodies, including antibodies to ABO blood group antigens, emerge after the contact of immune cells with the intestinal microbiota, which expresses a vast diversity of carbohydrate antigens. Here we explore the development of carbohydrate-specific antibodies in humans, addressing the definition of natural antibodies and the production of carbohydrate-specific antibodies upon antigen stimulation. We focus on the significance of the intestinal microbiota in shaping carbohydrate-specific antibodies not just in the gut, but also in the blood circulation. The structural similarity between bacterial carbohydrate antigens and surface glycoconjugates of protists, fungi and animals leads to the production of carbohydrate-specific antibodies protective against a broad range of pathogens. Mimicry between bacterial and human glycoconjugates, however, can also lead to the generation of carbohydrate-specific antibodies that cross-react with human antigens, thereby contributing to the development of autoimmune disorders.

Topics: Animals; Antibodies; Antigen Presentation; Autoimmunity; Carbohydrates; Gastrointestinal Microbiome; Glycoconjugates; Humans

PubMed: 32753697
DOI: 10.1038/s41435-020-0105-9

Authors: Nicola L B Pohl

Topics: Carbohydrates; Chemical Phenomena; Chemistry, Organic

PubMed: 30205688
DOI: 10.1021/acs.chemrev.8b00512

Review

Authors: Nikolai Petrovsky, Peter D Cooper

The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum's relative monopoly. To seriously challenge alum's supremacy a new adjuvant has many major hurdles to overcome, not least being alum's simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum's monopoly over human vaccine usage.

Topics: Adjuvants, Immunologic; Bacteria; Carbohydrates; Humans; Plants; United States; Vaccines; Yeasts

PubMed: 21506649
DOI: 10.1586/erv.11.30

Review

Authors: Sungjin Park, Jeffrey C Gildersleeve, Ola Blixt...

In the last decade, carbohydrate microarrays have been core technologies for analyzing carbohydrate-mediated recognition events in a high-throughput fashion. A number of methods have been exploited for immobilizing glycans on the solid surface in a microarray format. This microarray-based technology has been widely employed for rapid analysis of the glycan binding properties of lectins and antibodies, the quantitative measurements of glycan-protein interactions, detection of cells and pathogens, identification of disease-related anti-glycan antibodies for diagnosis, and fast assessment of substrate specificities of glycosyltransferases. This review covers the construction of carbohydrate microarrays, detection methods of carbohydrate microarrays and their applications in biological and biomedical research.

Topics: Antibodies, Monoclonal; Bacterial Proteins; Biomarkers; Carbohydrates; Humans; Lectins; Microarray Analysis; Polysaccharides; Viral Proteins

PubMed: 23192235
DOI: 10.1039/c2cs35401b

Authors: Juan Luis Asensio, Ana Ardá, Francisco Javier Cañada...

The recognition of saccharides by proteins has far reaching implications in biology, technology, and drug design. Within the past two decades, researchers have directed considerable effort toward a detailed understanding of these processes. Early crystallographic studies revealed, not surprisingly, that hydrogen-bonding interactions are usually involved in carbohydrate recognition. But less expectedly, researchers observed that despite the highly hydrophilic character of most sugars, aromatic rings of the receptor often play an important role in carbohydrate recognition. With further research, scientists now accept that noncovalent interactions mediated by aromatic rings are pivotal to sugar binding. For example, aromatic residues often stack against the faces of sugar pyranose rings in complexes between proteins and carbohydrates. Such contacts typically involve two or three CH groups of the pyranoses and the π electron density of the aromatic ring (called CH/π bonds), and these interactions can exhibit a variety of geometries, with either parallel or nonparallel arrangements of the aromatic and sugar units. In this Account, we provide an overview of the structural and thermodynamic features of protein-carbohydrate interactions, theoretical and experimental efforts to understand stacking in these complexes, and the implications of this understanding for chemical biology. The interaction energy between different aromatic rings and simple monosaccharides based on quantum mechanical calculations in the gas phase ranges from 3 to 6 kcal/mol range. Experimental values measured in water are somewhat smaller, approximately 1.5 kcal/mol for each interaction between a monosaccharide and an aromatic ring. This difference illustrates the dependence of these intermolecular interactions on their context and shows that this stacking can be modulated by entropic and solvent effects. Despite their relatively modest influence on the stability of carbohydrate/protein complexes, the aromatic platforms play a major role in determining the specificity of the molecular recognition process. The recognition of carbohydrate/aromatic interactions has prompted further analysis of the properties that influence them. Using a variety of experimental and theoretical methods, researchers have worked to quantify carbohydrate/aromatic stacking and identify the features that stabilize these complexes. Researchers have used site-directed mutagenesis, organic synthesis, or both to incorporate modifications in the receptor or ligand and then quantitatively analyzed the structural and thermodynamic features of these interactions. Researchers have also synthesized and characterized artificial receptors and simple model systems, employing a reductionistic chemistry-based strategy. Finally, using quantum mechanics calculations, researchers have examined the magnitude of each property's contribution to the interaction energy.

Topics: Carbohydrates; Drug Design; Hydrocarbons, Aromatic; Hydrogen Bonding; Models, Molecular; Monosaccharides; Proteins; Thermodynamics; Water

PubMed: 22704792
DOI: 10.1021/ar300024d

Review

Authors: Elżbieta Wojaczyńska, Franz Steppeler, Dominika Iwan...

Organocatalysis is a very useful tool for the asymmetric synthesis of biologically or pharmacologically active compounds because it avoids the use of noxious metals, which are difficult to eliminate from the target products. Moreover, in many cases, the organocatalysed reactions can be performed in benign solvents and do not require anhydrous conditions. It is well-known that most of the above-mentioned reactions are promoted by a simple aminoacid, l-proline, or, to a lesser extent, by the more complex cinchona alkaloids. However, during the past three decades, other enantiopure natural compounds, the carbohydrates, have been employed as organocatalysts. In the present exhaustive review, the detailed preparation of all the sugar-based organocatalysts as well as their catalytic properties are described.

Topics: Carbohydrates; Catalysis; Epoxy Compounds; Monosaccharides; Oxidation-Reduction; Polysaccharides

PubMed: 34885873
DOI: 10.3390/molecules26237291