Preface [Hot topic: Carbohydrates (Executive Editor: Istvan Toth)]

The last few years have witnessed an explosion of interest in the area of carbohydrates in biology and medicinal chemistry. Carbohydrates are among the most important class of molecules in biological systems and are at the centre of an enormous amount of modern pharmaceutical research, particularly in the areas of cancer, immunotherapy, infection and inflammation. Glycoproteins, because they are localized on the cell surface, play key roles in cell-cell and cell-pathogen interactions, recognition events and signal transduction. Mimetics of these glycoconjugates are therefore likely to be important candidates for future drug development. Carbohydrates represent one of the major components of the outer surface of mammalian cells, the outer cell membrane being studded with glycoproteins and glycolipids. While the roles of most of these species remain to be elucidated, we already know that different glycosylation patterns are associated with different stages of cell development, and that pathological states, such as cancers, can lead to abnormal alterations in cell-surface glycosylation. The appending of sugars onto proteins alters many of their biochemical properties, such as secondary and tertiary conformations, and resistance to proteases. The introduction of faster computers and better software has seen an increase in interest in the modelling of these highly flexible carbohydrates and glycoconjugates, with the aim of designing new carbohydrate-based drugs. The chemical synthesis of carbohydrates and carbohydrate-like molecules, particularly complex polysaccharides and glycoconjugates, is often very challenging. Nevertheless, chemical synthesis allows us to secure pure and homogeneous material that is otherwise very difficult to obtain from biological sources. Additionally, we can obtain by synthesis molecules with modified physicochemical characteristics, with resulting improvements in stability towards degrading enzymes and to the gastric environment. The synergistic interactions between synthetic chemists and glycoscientists have resulted in advances in both areas. Some of the disadvantages of using carbohydrates as drugs are well known, such as their (often) poor uptake, low affinity for receptors and poor biostability. However, in spite of the perception that carbohydrates do not make good drugs, there are in fact many such drugs currently used as therapeutics, and many more in clinical trials. These include pharmaceuticals used to treat conditions such as influenza, arthritis, inflammatory diseases, cancer and epilepsy. The advantages of using carbohydrates as therapeutics relative to, say, peptides, are their lower toxicity and immunogenicity. Advances in our understanding of carbohydrate-mediated biological processes, the design and synthesis of biologically active carbohydrate-based molecules, and efforts to overcome some of the current limitations of this class of compound, will undoubtedly lead to increased numbers of drugs in the pharmaceutical pipeline, for the treatment of a wide range of diseases. This issue of MRMC reviews the following aspects: - Molecular modelling of carbohydrates; - The effects of glycosylation on the conformations of peptides; - The identification of polysaccharide biosynthesis inhibitors as new anti-tuberculosis agents; - The design of inhibitors of the carbohydrate-binding proteins, selectins; - A survey of the diverse structural types of glycosidase inhibitors; - The physicochemical characteristics of carbohydrate-based drugs; - Chemoselective synthesis of neoglycoconjugates; - Drug development based on heparin-protein interactions.