Preface [Hot Topic: Complex Carbohydrates (Guest Editors: Nasir-ud-Din and Daniel C. Hoessli)]

The present issue of Current Organic Chemistry, “ Complex Carbohydrates” consists of six reviews on complex carbohydrate structures that modify proteins and lipids. The authors of these articles are leading researchers in the areas of glycan structure / function relationships and have performed pioneering studies on glycoproteins, proteoglycans and glycosphingolipids. The first review by Professor G.W Hart's group is entitled “Nucleocytoplasmic Glycosylation, O-linked β-NAcetylglucosamine” and describes the nature, localization, structure and possible roles for O-GlcNAc modifications in specific cellular pathways including signal transduction, nuclear transport, transcription, protein metabolism, apoptosis and functions performed by cytoskeletal proteins. This review further describes the interplay of the O-GlcNAc modification with phosphorylation. The authors also deal with the implications of the O-GlcNAc modification in dysregulated cellular processes leading to hyperglycemia, obesity, type II-diabetes, cancer and neurodegeneration. The second review by Professor M.C. Glick's group is concerned with “The Glycobiology of Cystic Fibrosis”. The review focuses on Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in pulmonary epithelial cells. The CFTR, a glycoprotein acting as a Cl- channel is extensively modified by repeating units of N-acetyllactosamine. The glycosylated CF airway epithelial cell exhibits a glycophenotype characterized by increased expression of fucosyl residues and / or decreased expression of sialic acid. This review further elaborates on the possibility of compartmental differences in the Golgi between CF and non-CF glycosyltransferases for the generation of CF glycophenotypes. The third article, entitled “Relationships of Connective Tissue Glucosaminoglycans and Proteoglycans” is by Professor J.E. Silbert, who describes the nature and structure of connective tissue proteoglycans containing the linear polysaccharide (glucosaminoglycan) hyaluronan, glucosaminoglycan chondroitin / dermatan sulfate and keratan sulfate. Matrix proteoglycans are classified into two groups, namely the “hyalectins” and the SLRP (small leucine-rich proteins). Furthermore, the review provides information about the structure, biosynthesis, degradation and turnover, classification, distribution and function of different glycans in connective tissue glucosaminoglycans and proteoglycans. In addition to their glycosylation, the phosphorylation and sulfation of such macromolecules is also considered within the context their biosynthesis. The fourth review by Professors Ph. Roussel and P. Delmotte deals with “ The Diversity of Epithelial Secreted Mucins ” in human, amphibian and fish epithelia. These mucins are heavily glycosylated, wherein the O-linked glycans make up to 80% of the mucin molecular mass. Furthermore, multimerization of mucins via disulfide bridges occurs during biosynthesis and generates biomolecules of highest complexity. The review also covers the general properties, diversity in types and post-translational modifications of secreted mucins in different vertebrate subgroups. The secand last article by Professor D.C. Hoessli and co-workers is entitled “Glycosphingolipid Clusters as Organizers of Plasma Membrane Rafts and Caveolae”. This review described the contribution of glycosphingolipids in the organization of plasma membrane rafts and caveolae, thus building up a new vision of membrane organization and function. For instance, the role of rafts and caveolae in signal transduction, adhesion, endocytosis and entry of microbial pathogens is discussed. Lastly, the use of rafts and caveolae as therapeutic targets in the treatment of metabolic diseases and cancer is discussed. The last article by Professor Nasir-ud-Din deals with “Combinatorial Metabolism in Plasmodium falciparum-infected Erythrocytes and Interplay and Glycosylation and Phosphorylation”. The review proposes the concept of combinatorial metabolism in the P. falciparun-infected erythrocyte and develops this concept regarding the glycosylation and phosphorylation of MSP-1 and other parasitic proteins, a process in which catalysis of such modifications is carried out by host-cell enzymes acting upon parasitic proteins. Furthermore, the functional consequences of one amino acid modification by a glycan or a phosphate are discussed for specific parasitic proteins.