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Protein and lipid glycosylation is a ubiquitous phenomenon. The task of cataloguing the great structural variety of the glycan part has demanded considerable efforts over decades. This patient endeavor was imperative to discern the inherent rules of glycosylation which cannot affirm assumptions on a purely coincidental nature of this type of protein and lipid modification. These results together with theoretical considerations uncover a salient property of oligosaccharides. In comparison with amino acids and nucleotides, monosaccharides excel in their potential to serve as units of hardware for storing biological information. Thus, the view that glycan chains exclusively affect physiochemical properties of the conjugates is indubitably flawed. This original concept has been decisively jolted by the discovery of endogenous receptors (lectins) for distinct glycan epitopes which are as characteristic as a fingerprint or a signature for a certain protein (class) or cell type. Recent evidence documents that these binding proteins are even endowed with the capacity to select distinct low-energy conformers of the often rather flexible oligosaccharides, granting entry to a new level of regulation of ligand affinity by shifting conformer equilibria. The assessment of the details of this recognition by X-ray crystallography, nuclear magnetic resonance spectroscopy, microcalorimetry and custom-made derivatives is supposed to justify a guarded optimism in satisfying the need for innovative drug design in antiadhesion therapy, for example against viral or bacterial infections and unwanted inflammation. This review presents a survey of the structural aspects of glycosylation and of evidence to poignantly endorse the notion that carrier-attached glycan chains can partake in biological information transfer at the level of cell compartments, cells and organs.

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Sialylated oligosaccharides, which are cell type-specific and developmentally regulated, have been implicated in a variety of complex biological events. Their broad functional importance is reflected by their presence in a wide variety of phyla extending from Echinodermata through higher vertebrates. Here, sialic acids are detected throughout development in an insect, Drosophila. Homopolymers of alpha 2,8-linked sialic acid, polysialic acid, are developmentally regulated and only expressed during early Drosophila development.

An overlay and a solid-phase assay are presented which allow the specific detection of 9-0-acetylated sialic acids on sialoglycoconjugates immobilized on microtiter plates, nitrocellulose or separated on thin-layer chromatograms. The assay takes advantage of two different biological properties of influenza C virus, its high-affinity binding to 9-0-acetylated sialic acids and its sialate 9-0-acetylesterase that is used for detection of bound virus with fluorogenic or chromogenic substrates. Though simple and rapid, the assay is highly sensitive with a detection limit of 65 fmol9-0-acetylated sialic acid in 9-0-acetylated ganglioside GDla.Influenza C virus is able to bind to a wide spectrum of sialoglycoconjugates like mucins, serum glycoproteins or gangliosides containing naturally or synthetically 0-acetylated sialic acids. 9-0-Acetyl-N-glycoloylneuraminic acid can also function as a high-affinity receptor determinant for influenza C virus. While the acetyl ester at the 9 position is essential for virus binding in all cases, a 4-0-acetyl group is not recognized. In addition to a(2,3) or a(2,6) bonds, 9-0-acetyl-N-acetylneuraminic acid in a(2,8) linkage to N-acetylneuraminic acid is also functionally active.Sialic acids are a Family of about 30 related sugars derived from neuraminic acid, which is the most diversely substituted sugar known in nature. This diversity mainly arises from acetylations that can take place at positions 4,7. 8, and/or 9. In most cases sialic acids occupy the terminal positions of glycoconjugates. Thcir involvement in many biological phenomena, especially as regulation of molecular and cellular recognition is concerned, has been well established [l]. In recent years, the interest in 0-acetylated sialic acids has rapidly increased, since some biological properties of these sugars seem to be associated with these modifications. Examples are the partial or complete block of sialidase action [2,3], binding of influenza C viruses and coronaviruses to cells [4, 51, antigenicity of bacterial capsules [6], modulation of the alternative pathway of complement activation [7], the expression of Nacetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) [8] as a differentiation marker on chicken erythrocytes [9], the association of 9-0-acetylated gangliosides with cell migration in rat brain development [lo], and the expression of an 0-acetylated Correspondence to R. Schauer, Biochemisches Institut, ChristianAlbrechts-Universitat, Okhausenslrasse 40, W-2300 Kiel, Federal Republic of Germany Abbreviution?. RSM, bovine submandibular gland mucin; DMB, 1,2-diamino-4,5-methylenedioxybenzene; ESM, equine submandibular gland mucin; GalNAc, N-acetylgalactosamine; Lac-Cer, lactosylceramide; McUmbAc, 4-methylumbelliferyl acetatc; Neu4,5Ac2, Nacetyl-4-O-acetylneuraminic acid; Neu4AcSGc. N-glycoloyl-4-O-acetylneuraminic acid; Neu5Ac, N-acctylneuraminic acid; Neu5,7Ac2, N-acetyl-7-0-acetylneuraminic acid; Neu5,9Ac2, N-acetyl-9-Oacetylneuraminic acid; NeuSAcgLt, N-acetyl-9-0-lactoylneuraminic acid; Neu9AcSGc, N-glycoloyl-9-0-ac...

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The conformation of the GM3 ganglioside, Neu5Ac alpha 2-3Gal beta 1-4Glc beta 1-1 Cer, and its analogs containing the Neu5Gc or Neu4Ac5Gc residues (Gc = glycolyl, CH2OHCO) was investigated in Me2SO-d6 solution with the aid of a distance-mapping procedure based on rotating-frame NOE contacts, with hydroxyl protons being used as long-range sensors defining the distance constraints. A pronounced flexibility found for both the Neu-Gal and Gal-Glc linkages was confirmed by 1000-ps molecular dynamics simulations. Similar results, although based on a smaller number of NOE constraints, were obtained for GM3 gangliosides anchored in mixed D2O/dodecylphosphocholine-d38 micelles and for the Neu5Ac-, Neu5Gc-, and Neu5,9Ac2-sialyllactoses dissolved in D2O. No noteworthy differences in conformational behavior of the glycan chains of the three gangliosides or sialyllactoses were observed in either of the media.

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