Advances in carbohydrate chemistry and biochemistry最新文献

Sialic acid-based glycoconjugates cover the surfaces of many different cell types, defining key properties of the cell surface such as overall charge or likely interaction partners. Because of this prominence, sialic acids play prominent roles in mediating attachment and entry to viruses belonging to many different families. In this review, we first describe how interactions between viruses and sialic acid-based glycan structures can be identified and characterized using a range of techniques. We then highlight interactions between sialic acids and virus capsid proteins in four different viruses, and discuss what these interactions have taught us about sialic acid engagement and opportunities to interfere with binding.

Gangliosides comprise a varied family of glycosphingolipid structures bearing one or more sialic acid residues. They are found in all mammalian tissues but are most abundant in the brain, where they represent the quantitatively major class of sialoglycans. As prominent molecular determinants on cell surfaces, they function as molecular-recognition partners for diverse glycan-binding proteins ranging from bacterial toxins to endogenous cell-cell adhesion molecules. Gangliosides also regulate the activity of plasma membrane proteins, including protein tyrosine kinases, by lateral association in the same membranes in which they reside. Their roles in molecular recognition and membrane protein regulation implicate gangliosides in human physiology and pathology, including infectious diseases, diabetes, cancer, and neurodegeneration. The varied structures and biosynthetic pathways of gangliosides are presented here, along with representative examples of their biological functions in health and disease.

Sialic acid (Sia) is involved in many biological activities and commonly occurs as a monosialyl residue at the nonreducing terminal end of glycoconjugates. The loss of activity of UDP-GlcNAc2-epimerase/ManNAc kinase, which is a key enzyme in Sia biosynthesis, is lethal to the embryo, which clearly indicates the importance of Sia in embryogenesis. Occasionally, oligo/polymeric Sia structures such as disialic acid (diSia), oligosialic acid (oligoSia), and polysialic acid (polySia) occur in glycoconjugates. In particular, polySia, a well-known epitope that commonly occurs in neuroinvasive bacteria and vertebrate brains, is one of the most well-known and biologically/neurologically important glycotopes in vertebrates. The biological effects of polySia, especially on neural cell-adhesion molecules, have been well studied, and in-depth knowledge regarding polySia has been accumulated. In addition, the importance of diSia and oligoSia epitopes has been reported. In this chapter, the recent advances in the study of diSia, oligoSia, and polySia residues in glycoproteins in neurology, and their history, definition, occurrence, analytical methods, biosynthesis, and biological functions evaluated by phenotypes of gene-targeted mice, biochemical features, and related diseases are described.

Sialic acids are cytoprotectors, mainly localized on the surface of cell membranes with multiple and outstanding cell biological functions. The history of their structural analysis, occurrence, and functions is fascinating and described in this review. Reports from different researchers on apparently similar substances from a variety of biological materials led to the identification of a 9-carbon monosaccharide, which in 1957 was designated "sialic acid." The most frequently occurring member of the sialic acid family is N-acetylneuraminic acid, followed by N-glycolylneuraminic acid and O-acetylated derivatives, and up to now over about 80 neuraminic acid derivatives have been described. They appeared first in the animal kingdom, ranging from echinoderms up to higher animals, in many microorganisms, and are also expressed in insects, but are absent in higher plants. Sialic acids are masks and ligands and play as such dual roles in biology. Their involvement in immunology and tumor biology, as well as in hereditary diseases, cannot be underestimated. N-Glycolylneuraminic acid is very special, as this sugar cannot be expressed by humans, but is a xenoantigen with pathogenetic potential. Sialidases (neuraminidases), which liberate sialic acids from cellular compounds, had been known from very early on from studies with influenza viruses. Sialyltransferases, which are responsible for the sialylation of glycans and elongation of polysialic acids, are studied because of their significance in development and, for instance, in cancer. As more information about the functions in health and disease is acquired, the use of sialic acids in the treatment of diseases is also envisaged.

Investigations of methodologies aimed on improving the stereoselective synthesis of sialosides and the efficient assembly of sialic acid glycoconjugates has been the mission of dedicated research groups from the late 1960s. This review presents major accomplishments in the field, with the emphasis on significant breakthroughs and influential synthetic strategies of the last decade.