Comparative Studies on the Structures of the Carbohydrate Moieties of Human Fibrinogen and Abnormal Fibrinogen Nagoya1

Mizuochi, Tsuguo; Taniguchi, Takahiro; Asami, Yoshio; Takamatsu, Junki; Okude, Masayoshi; Iwanaga, Sadaaki; Kobata, Akira

doi:10.1093/oxfordjournals.jbchem.a133925

Cited by 66 publications

(46 citation statements)

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“…the priinary structure of the two major glycans of bovine fibrinogen has been determined. The structures are identical to those of the two m;i.ior glycans A-1 and A-2 of human fibrinogen, except for thc presence o f N-glycolyl nueraniinic acid and the ratio of 2 for mono/disialylated glycans in human compared to 1 in bovine fibrinogen [11,351. The latter investigators applied 300-MHz 'H-NMR spectroscopy of fibrinogen glycopeptides, in combination with exoglycosidase treatment, a s the method of structural analysis.…”

Section: Discussionmentioning

confidence: 58%

Primary structure of two major glycans of bovine fibrinogen

Debeire¹,

Montreuil²,

Móczár³

et al. 1985

Eur J Biochem

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After pronase digestion of bovine fibrinogen, the asparagine-linked glycans were released from the resulting glycopeptides by hydrazinolysis, and subsequently re-N-acetylated. Two sialylated glycans wcrc isolated by ionexchange chromatography. Their primary structure has been determined by mcthylation analysis and 360-MHz 'H-NMR spectroscopy. The structures proposed to be present in the native glycoprotein are as follows:Fibrinogen and fibrin from a number of animal species are glycoproteins [I]. The biological role of their glycan moieties is not yet clear despite active investigations in this field. For example, it has been reported that neutral carbohydrates [2] or sialic acid [3] are released during clotting but a number of investigations were unable to confirm these results [4, 51. The decrease in coagulability of fibrinogen after periodate oxidation of glycans also suggested a role of the latter in the clotting process [6]. This finding has since been critized, as the reduction of the clotting time may be due to oxidation of some amino acid residues [7]. Recently, it was demonstrated that the enzymatic removal of glycans does not change the clotting time of fibrinogen [8].Study of pathological cases did not bring more information about the relationship between sugars and clotting. In fact congenitally abnormal fibrinogens [9 -1 I] have in some ciiscs a lower carbohydrate content than normal ones but is seems that the primary cause of these coagulation disturbances is an amino acid substitution. However, sialic-acidfree fibrinogen forms a gel different from the normal protein [I21 and yields urea-soluble fibrin in thc presence of factor XI11 [13]. Thesc findings suggest that the carbohydrate in fibrinogen could play a role in the complex polymerisation process.Attempts to clarify the structure of the glycan of bovine fibrinogen were done earlier by Mester et al. [ 14, IS], but due to the poor performances of the analytical methods used at that time, the authors did not obtain exact determination of the structure. The present paper describes the primary structure of the two major glycans of bovine fibrinogen deter-('orre.s/7:llonc(c./~~f~ to

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Section: Discussionmentioning

confidence: 58%

Primary structure of two major glycans of bovine fibrinogen

Debeire¹,

Montreuil²,

Móczár³

et al. 1985

Eur J Biochem

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“…High-voltage paper electrophoresis, Bio-Gel P-4 (extrafine) column chromatography and enzymic microsequencing procedures were performed according to procedures described previously [16,18,191.…”

Section: Methodsmentioning

confidence: 99%

“…Sialidase purified from Arthrobacter ureafaciens was purchased from Nakarai Chemicals Ltd (Kyoto, Japan). Digestions of radioactive oligosaccharides with glycosidases were performed as described previously [13,16]. Affinity columns of Ricinus communis agglutinin 120 (RCA-120) and of Phaseolus vulgaris erythrohaemagglutinin (E-PHA) coupled to agarose were from Vector Laboratories (Peterborough, UK) and concanavalin A (ConA) coupled to Sepharose from Pharmacia (Uppsala, Sweden).…”

Section: Chemicals and Enzymesmentioning

confidence: 99%

The spectrum of N‐linked oligosaccharide structures detected by enzymic microsequencing on a recombinant soluble CD4 glycoprotein from Chinese hamster ovary cells

Yuen¹,

Carr²,

Feizi³

1990

European Journal of Biochemistry

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Structures of the N-linked oligosaccharides of a recombinant soluble form of human CD4 glycoprotein (sCD4) have been investigated by enzymic microsequencing. The glycoprotein has two N-glycosylation sites, Asn271 and Asn300, at both of which evidence for the presence of complex type biantennary sialo-oligosaccharides has been obtained previously by mass spectrometric analyses [Carr, S. A., Hemling, M. E., Folena-Wasserman, G., Sweet, R. W., Anumula, K., Barr, J. R., Huddleston, M. J. & Taylor, P. (1989) J . B i d . Chem. 264,21286-21 2951. Among oligosaccharides released from sCD4 by hydrazinolysis and labelled with NaB3H4, neutral (12.8%) and acidic (87.2%) oligosaccharides were detected by paper electrophoresis. The latter were rendered neutral following sialidase treatment indicating that acidity was due exclusively to the presence of sialic acid residues. By enzymic microsequencing of the sialidase-treated oligosaccharides (fractionated on affinity columns of Ricinis communis agglutinin 120 and concanavalin A) in conjunction with methylation data from the earlier study, 14 sequences were identified. These accounted for over 80% of the sialidase-treated oligosaccharides of sCD4 as follows : fFucal Gal@l-4GlcNAcpl-2Manal

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“…The oligosaccharides present in the IgG-Fc of normal polyclonal IgG, attached at Asn 297, are of the complex diantennary type and comprised of a core heptasaccharide with variable addition of fucose, galactose, bisecting N-acetylglucosamine and sialic acid; sialylation is modest with º10z of structures being monosialylated or disialylated (4,(17)(18)(19)(20). The relative yields and structure of the neutral oligosaccharides released from normal IgG-Fc are shown in Figs.…”

Section: Glycoform Proˆles Of Normal Serum Derived Igg In Health mentioning

confidence: 99%

Glycoforms of Human IgG in Health and Disease

Jefferis¹

2009

TIGG

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More than twenty recombinant antibody molecules are now licensed for treatment of a variety of cancers and chronic diseases. In addition there are, literally, hundreds in development and early phase clinical trials. Initially, the attraction of antibodies was their speciˆcity for target antigens; however, it is now appreciated that the immune complexes formed trigger downstream biological activities that are critical to clinical success. It has been demonstrated that, although accounting for only 2-3z of antibody mass, glycosylation of the IgG-Fc is essential to the activation of such biologic mechanisms (eŠector functions). Additionally the precise structure of the attached oligosaccharide can determine protein conformation and stability and hence downstream biologic e‹cacy. Cellular engineering has been embraced to generate cell lines that synthesise selected homogeneous antibody glycoforms that may be optimal for a given disease indication. The advantage of being able to formulate therapeutic antibody preparations at high concentration might be aided by additional glycosylation within the IgG-Fab region. Novel production vehicles are also being developed that oŠer the possibility of lower production costs, with consequent lower cost of goods.

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Comparative Studies on the Structures of the Carbohydrate Moieties of Human Fibrinogen and Abnormal Fibrinogen Nagoya1

Cited by 66 publications

References 0 publications

Primary structure of two major glycans of bovine fibrinogen

Primary structure of two major glycans of bovine fibrinogen

The spectrum of N‐linked oligosaccharide structures detected by enzymic microsequencing on a recombinant soluble CD4 glycoprotein from Chinese hamster ovary cells

Glycoforms of Human IgG in Health and Disease

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