A large proportion of patients with failing heart, liver or kidney, do not receive the needed organ because of an insufficient number of organ donors. As a result of this shortage in allografts, pig xenografts have been considered as an alternative source of organs for transplantation. The major obstacle currently known to prevent pig to human xenotransplantation is the interaction between the human natural anti-Gal antibody and the α-gal epitope(Galα1-3Galβ1-4GlcNAc-R), abundantly expressed on pig cells. This epitopes is expressed on pig and other mammalian cells, but is absent in humans because of the evolutionary inactivation of the α1, 3galactosyltransferase gene in ancestral primates. In this review, we describe the characteristics of anti-Gal and of the α-gal epitope, their role in inducing xenograft rejection and some of the theoretical approaches for preventing this rejection.

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Selectin is a family of cell adhesion molecules expressed on endothelial cells, leukocytes and platelets. It is implicated in extravasation of leukocytes, homing of lymphocytes, and infiltration or metastasis of malignant cells including leukemia cells and cancer cells. Sialyl Lewis x, sialyl Lewis a and several other carbohydrate determinants have been known to serve as carbohydrate ligands for selectins. The most-recently described selectin ligand is sialyl 6-sulfo Lewis x. This determinant was first described as a major lymphocyte homing receptor for L-selectin expressed on high endothelial venules of human lymph nodes, and later found to be expressed on certain subsets of lymphocytes and on some cells of epithelial origin, calso serving as a ligand for E- and/or P-selectin. Expression of sialyl 6-sulfo Lewis x is regulated differently from that of conventional sialyl Lewis x in that it is metabolized through a distinct metabolic pathway involving the cyclization of sialic acid moiety. In this article we will review the distribution, csynthesis and metabolic fate of this new selectin ligand, and discuss its physiological significance.

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Some patients have developed Guillain-Barré syndrome after the administration of bovine brain ganglioside. Patients with Guillain-Barré syndrome subsequent to Campylobacter jejuni enteritis frequently have the IgG antibody to GM1 ganglioside. Miller Fisher syndrome, a variant of Guillain-Barré syndrome, is associated with IgG antibody to GQ1b ganglioside. My colleagues and I showed the existence of molecular mimicry between GM1 and the lipopolysaccharide of C. jejuni isolated from a patient with Guillain-Barré syndrome, and between GQ1b and C. jejuni lipopolysaccharides from patients with Miller Fisher syndrome. The glycotope mimicry between infectious agents and gangliosides may function in the production of anti-ganglioside antibodies and the development of Guillain-Barré syndrome and Miller Fisher syndrome.

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O-GlcNAcylation of nucleoplasmic and cytoplasmic proteins is a ubiquitous and highly dynamic modification. It entails the attachment of a single O-linked N-acetylglucosamine (O-GlcNAc) moiety O-glycosidically linked to side-chain hydroxyls of serine and threonine residues. The rapidly expanding list of O-GlcNAcylated proteins includes RNA Polymerase II, nuclear pore, heat shock, and tumor suppressor proteins, nuclear oncogenes, and numerous cytoskeletal and membrane associated proteins. Many sites of O-GlcNAc addition are similar to consensus sites of protein phosphorylation, and in some cases identical. Accordingly, O-GlcNAcylation and O-phosphorylation appear to be reciprocally related on some proteins. All O-GlcNAcylated proteins are phosphoproteins which assemble into tightly regulated reversible multi-protein complexes. Several O-GlcNAcylated proteins are key components involved in cytoskeletal assembly and organization, and defects in their regulated multimerization are implicated in several neurodegenerative disorders. Thus, abnormal cytoskeletal O-GlcNAcylation may promote defects in regulated protein multimerization and potentiate disease.

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α2→8-Linked di- and oligosialic acid (diSia and oligoSia) chains with DP 2, 3 Sia residues are known to be common structural units of gangliosides, and to be involved in various biological processes, such as cell adhesion, cell differentiation, signal transduction, and surface expression of stage specific antigen. In contrast, little attention has been paid to the occurrence and functions of such short sialyl oligomers on glycoproteins. However, it has recently been shown that glycoproteins containing di- and oligoSia groups occur in nature more frequently than was ever recognized, as analytical methods to detect di- and oligoSia structures have improved. It is thus hypothesized that these di- and oligoSia moieties on glycoproteins may have similar important functions in common with those proposed for the gangliosides. In this review, we describe the recent advances in the study of di- and oligoSia residues on glycoproteins, including analytical methods, occurrence, functions, and biosynthetic pathways.

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The author describes investigations on ABO and Lewis blood-group antigens from the time in the 1940s when practically nothing was known about their chemical structure until today when the genes ultimately responsible for the appearance of the antigens on the red blood cell surface have been defined in molecular terms. The early work was carried out on glycoproteins in secretions that have the same serological specificity as the A, B, H, and Lewis antigens on red cells. Indirect methods of inhibition of haemagglutination with simple sugars and inhibition of degradation with exo-glycosidases led to the identification of the immunodominant sugars in the determinant structures. The sequential degradation with exo-glycosidases established the precursor-product relationship of A and B to H and showed that a single sugar masked the underlying specific H structure. Fragmentation of the purified glycoproteins with mild acid or alkali led eventually to defined structures for the five specificities A, B, H, Le(a) and Le(b). Knowledge of the chemical basis of the blood-group reactions enabled schemes to be proposed for the genetic control and biosynthesis of the glycoproteins that explained the interactions at the phenotypic level between the ABO, H, Secretor and Lewis genes. The proposal that the primary protein products of the blood-group genes are glycosyltransferase enzymes that transfer the immunodominant sugar to complete the determinant structures was confirmed and the characterization of these glycosyltransferases has enabled the blood-group genes to be cloned and sequenced by others. Studies on the P₁ determinant in the blood-group P system and the Sd(a) determinant in the Sid system were also performed on soluble sources of material that carried the same specificity as the antigens on the red cell surface. A glycoprotein isolated from sheep hydatid cyst fluid yielded the structure of the P₁ determinant and the structure of the Sd(a) determinant was identified amongst fragments released from Tamm-Horsfall glycoprotein which is secreted in soluble form in human urine.

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The field of glycobiology in allergen research is emerging. Plant N-linked oligosaccharides of complex type generally possess a characteristic core structure with xylose β1-2 linked to β-mannose and fucose α1-3 linked to N-acetylglucosamine at the reducing end, which rarely found in animals. Such glycans of plant glycoproteins have been found to induce immunogenic responses in animals. This brief review introduces the current knowledge on the structure, antigenicity and allergenicity of plant carbohydrate epitopes (plant glycotopes) obtained from the increasing number of studies on pollen and food allergens. It also presents some fundamental problems that must be elucidated for development of the glycobiology of plant glycotopes and application of the results to the treatment of allergy.

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3DinSight (http://www.rtc.riken.go.jp/3DinSight.html) is an integrated database and search tool of biomolecules. It has been developed to help researchers get an insight into the relationship between the structure, property and function of biomolecules. 3DinSight consists of an integrated database with a 3D structure, property and functional information on proteins, a set of search programs, a WWW interface and visualization tools. Fig. 1 shows the home page of 3DinSight.

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