A-glycan

Location of the Position of Attachment of a Glycan on the Polypeptide Backbone of a Glycoprotein... 

Yuen, C.T., Stoning, P.L., Tiplady, R.J. et al. (2003) Relationships between the A-glycan structures and biological activities of recombinant human erythropoietins produced using different culture conditions and purification procedures. British Journal of Haematology, 121 (3), 511-526. 

Fig. 15.1. The A/-glycan biosynthetic pathway, illustrating how the three classes of A/-glycans (high mannose, hybrid and complex glycans) are derived from a common biosynthetic precursor. The trimannosyl-chitobiose core, which is common to all A/-glycans, is outlined on the precursor A/-glycan. Glc, o Man, GIcNAc.

A fourth family of A-glycans are referred to as hybrid glycans. These glycans share structural features of the high mannose and complex-type families. They usually retain two mannoses on the 6-arm of the trimannosyl core whilst complex-type antennae are elaborated on the 3-arm. Hybrid structures are frequentiy bisected and may also be core fucosylated (Fig. 15.1). It should be noted that whilst core fucosylation is common in complex-type, hybrid and truncated glycans, it is rarely found in high mannose glycans. 

Novel Fucosylated A/-glycan Core Structures in Haemonchus contortus... 

Another interesting observation is that several species of filarial nematodes have been shown to express chitinase (Fuhrman, 1995). Indeed the chitinase of A. viteae infective stage larvae (L3) is the main target of the protective humoral immune response when jirds are vaccinated with irradiated attenuated L3s (Adam et al., 1996 see also Chapter 10). It remains to be established whether there is an interaction between the parasite s oligo-chitin A-glycans and chitinase and whether such an interaction has a role to play in parasite-host interaction. 

Haslam, S.M., Houston, KM., Harnett, W., Reason, A.J., Morris, H.R. and Dell, A. (1999) Structural studies of phosphorylcholine-substituted A-glycans of filarial parasites conservation amongst species and discovery of novel chito-oligomers. Journal of Biological Chemistry 274, 20953-20960. 

Figure 7.15 The reducing end of a glycan or a carbohydrate can be used to conjugate to an amine-dendrimer by reductive amination, which results in the formation of a secondary amine linkage.

Similar results were recently obtained with a human monoclonal antibody, with KDEL sequences fused to the C-termini of both heavy chains, expressed in tobacco [33]. As observed for the invertase-HDEL fusion, about 90% of the N-linked glycans on this antibody were of the high-mannose type, with 6-9 mannose residues, while a fraction contained the immunogenic P(l,2)-xylose glyco-epitope (Fig. 15.6). However, this antibody was not a(l,3)-fucosylated, a glycan modification occurring in the trans Golgi [34]. 

Also in the PP, associated with the CM, one can find the murein sacculus (for a review see [8]). This network is formed by the macromolecule pepti-doglycan, which confers the characteristic cell shape and provides the cell with mechanical protection. Peptidoglycans are unique to prokaryotic organisms and consist of a glycan backbone of N-acetylated muramic acid and N-acetylated glucosamine and cross-linked peptide chains [9-13]. 

Figure 10.3 Whole-mass analysis of a monoclonal antibody. (A) Direct infusion of the antibody generates an envelope of high m/z ions ranging from 2000 to 3500. Deconvolution of the ion current signal gives the mass of the complete native molecule (147, 100.97 Da) and resolves some heterogeneity linked to the A-glycan structures. The major forms are consistent with molecules carrying biantennary structures capped with 0, 1, or 2 hexose (G = galactose) residues. (Data generated on an ESI-Q-Star instrument, Sciex-Applied Biosystems.)...

Koprivova A, Stemmer C, Altmann F, Hoffmann A, Kopriva S, Gorr G Reski R, Decker EL. (2004) Targeted knockouts of Physcomitrella lacking plant-specific immunogenic A-glycans. Plant Biotechnol J 2 517-523. 

Two other structurally characterized transferases have the same or almost the same mode of Mn + coordination as Mn + in Bacillus subtilis glycosyltransferase SpsA described above. A-acetylglucosaminyltransferase I which serves as the gateway from oligomannose to hybrid and complex A-glycans and plays a critical role in mammalian development, has the same active site structure except the Mg + ion and the glycerol are not present. /3 1,3-Glucuronyltransferase I... 

There is a clear distinction between exo- and endo-glycosidases the former act at the nonreducing end of a glycan chain, whereas the latter cleave at some point along an oligosaccharide chain, either at random or in a chemical environment -specific manner. 

We had for some time considered that aziridines, because of their increased basicity and hence reactivity at the active site of a glycan hydrolase, would prove to be better inhibitors than the epoxides in many respects. Conversely, the less basic thiirans would be expected to be poorer inhibitors than the corresponding epoxides. We thus embarked on a synthesis of the aziridine 30 and the thiiran 31. 

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