Eukaryotic glycosylation: whim of nature or multipurpose tool?

Abstract

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.

Binding Sites for Lewis Antigens Are Expressed by Human Colon Cancer Cells and Negatively Affect Their Migration

“…Upon sialylation or sulfation, a crucial contact point for selectin interaction is established (Angata and Varki, 2002;Fukuda et al, 1999;Reuter and Gabius, 1999;Varki 1997;Vestweber and Blanks, 1999). Figure 1A details the modular structures of selectins, and Figure 1B gives the schematic structures of known selectin-binding glycoproteins.…”

“…We thus used these neoglycoconjugates to identify the status and modifications occurring at the level of carbohydrate receptors, a crucial step in the functional study of lectinomics. Because selectin binding to sialylated Lewis antigens, as with other C-type activities, is calcium dependent (Reuter and Gabius, 1999;Varki, 1997), we also checked whether modification of the calcium concentration in the culture medium significantly modified the Lewis antigen-mediated influences on human colon cancer cell migration. Figure 2, A and C, serve as further internal controls for specificity of the underlying recognition process.…”

Alcohol abuse and glycoconjugate metabolism

“…The glycan chains of glycoproteins are nearly always covalently linked to functional groups of amino acid side chains within a protein (GlcNAcb1-Asn in N-glycans and GalNAca1-Ser or -Thr in O-glycans) [26]. The protein moiety of glycoprotein is synthesized in rough endoplasmatic reticulum ( Figure 1) [27].…”

“…The synthesis of O-glycosidically linked saccharide chains requires individual nucleotide-activated monosaccharides added by site-specific glycosyltransferases in a stepwise manner [26]. Properly folded glycoproteins are transported along microtubules, due to vesicular transport by microtubule directed motor complex of dynein/dynactin or kinesin, to the pre-Golgi compartment.…”

Synthesis of esters derived from 2,3,4,6-tetra-O-acetyl-1-[4-(2-hydroxyethyl)-1H-1,2,3-triazol-1-yl]-β-D-glucopyranose

“…The sugar moiety influences the drug molecules behavior and enhances the transport through cell membranes [17][18][19][20]. In a similar way to that observed in nature, chemists have been using carbohydrate scaffolds, to obtain libraries of compounds for screening in drug research [21].…”