O-Mannosylation

Glycolipid 2-a-mannosyltransferase [EC 2.4.1.131] catalyzes the transfer of an a-o-mannosyl residue from GDP-mannose into a lipid-Unked ohgosaccharide, forming an a-l,2-D-mannosyl-D-mannose hnkage. The two 1,2-linked mannosyl residues in the mammalian hpid-lmked... 

A comparison of direct O-mannosylation of serine or threonine on resin-bound peptides, with the incorporation of mannosylated serine or threonine building blocks, resulted in a higher overall yield for the building block approach (12.5 vs 5% for direct condensation). 134 Later it was demonstrated that resin-bound peptides are able to be glycosylated with different glycosyl trichloroacetimidates without protection of the hydroxy groups of the oligosaccharide moiety (Section 6.3.2.8). 135,136 ... 

Mannosides of phosphatidylinositol are important serologically active components of Mycobacterium tuberculosis. For the synthesis of the 2-O-mannosyl derivative (421), Stepanov et al. [291] treated the chiral prop-l-enyl ether (414) [and the corresponding racemic prop-l-enyl ether and racemic benzoate (415)] with the orthoesters (416) or (417) to give the disaccharide (418) [from chiral (414) and acetate (416)] in moderate yield. The disaccharide obtained from racemic (414) contained a high proportion of (418) as a result of asymmetric synthesis. Acidic hydrolysis of (418) gave in low yield (30%) the alcohol (419). 

Andrews, D. and Seale, P. (1993) Solid-phase synthesis of O-mannosylated peptides two strategies compared. Int. J. Pept. Protein Res. 42,165-170. 

Chiba A, Matsumura K, Yamada H, Inazu.T, Shimizu T, Kusunoki S, Kanazawa 1, Kobata A, Endo T. Stmctures of sialylated O-linked oligosaccharides of bovine peripheral nerve a-dystroglycan the role of a novel O-mannosyl-type oligosaccharide in the binding of a-dystroglycan with laminin. J. Biol. Chem. 1997 272(4) 2156-2162. 

The selective preparation of 1,2-czs-linkages in the D-manno and L-rhamno series is still one of the major challenges in oligosaccharide synthesis. Several new and promising approaches deal with this problem [59]. Since a number of pyru-vated oligo- and polysaccharides also contain o-mannosyl and j -L-rhamnosyl residues (Table 1), eCBcient strategies for their preparation are also needed here. 

Figure 5 Other types of O-linked glycosylation in eukaryotes, (a) O-Mannosylation (b) O-fucosylation (c) O-glucosylation (d) O-galactosylation.

A distinct feature that may not be readily noticeable is that the chemical shift of the C-1 atom of an Oi-D-mannosyl residue is highly dependent on its residue linkage to another a-o-mannosyl unit. The chemical shift for C-1 of an Oi-D-mannosyl linked to 0-2 or 0-3 of another a-o-mannosyl residue resonates at 103.5 p.p.m., whereas that of an a-o-mannosyl residue linked to 0-6 of another a-o-mannosyl unit will resonate at — 100.6 p.p.m. Moreover, if 0-2 of an a-o-mannosyl residue is glycosylated, the chemical shift of C-1 of that residue will move —1.5 p.p.m. from its expected position. 

Y., Nakagawa, X. et td. (2007) Efficient antibody production upon suppression of O-mannosylation in the yeast Ogataea minuta. Appl Environ. Microbiol, 74, 446-453. 

Snowdrop Galanthus nivalis Non-reducing terminal end of a-o-mannosyl... 

Orchard et al. [27] have s)mthesized rhodanine-3-acetic acid derivatives XVI, XVn, and XVIII inhibit Candida albicans PMTl with inhibition concentration 50% (IC50) values 0.17,0.2, and 0.35 pM, respectively. These compounds could serve as useful tools for studjdng the effects of protein O-mannosylation and its relevance in the search for novel antifungal agents. 

The presence on alveolar macrophages of a cell surface receptor that binds glycoproteins having terminal o-mannosyl- or o-glucosyl-units has been described. An assay system was developed for the measurement of the binding by cells. 

Isolated rough and smooth microsomes and Golgi membranes from the rat are able to incorporate o-mannosyl residues into endogenous protein acceptors, the final products being membrane proteins rather than secretory proteins. Part of the o-mannosyltransferase system is localized on the cytoplasmic side of the membranes. 

Membrane preparations from lactating bovine mammary glands have been shown to incorporate o-mannose from GDP-o-mannose into lipid and into metabolically stable acceptors." It is postulated that the sequence GDP-o-mannose P -D-mannosyl-P -pyrophosphorylisoprenol P -o-mannosyl-oligosaccharide-P -pyrophosphoryl o-mannoprotein is followed. The structure of the oligosaccharide-lipid and the endogenous glycoproteins were not established. 

A study of the interaction of a number of immunoglobulin-derived gjyco-peptides with concanavalin A has shown that the binding depends on terminal 2-acetamido-2-deoxy-j8-D-glucosyl and a-o-mannosyl residues and on internal D-mannosyl residues substituted at C-2. The saccharide-binding site seems to be capable of binding several sugar residues. The inhibition indexes of several... 

The mechanism of action of a-D-mannosidase has been discussed. Oligosaccharides containing terminal, non-reducing a-(l -> 2)-, oc-(l 3)-, and a-(l 6)-linked o-mannosyl residues, which were isolated from the urines of humans and cattle with mannosidosis, have been used to ascertain the substrate specificities of acid a-D-mannosidases obtained from human and bovine livers. Differences in the activities of A and forms of the enzyme were shown with all substrates. The C form (pH optimum ca. 7) did not hydrolyse any of the oligosaccharides at neutral pH, but it was active at a lower pH. 

The structure of one of the carbohydrate moieties of an a-amylase from a Rhizopus species has been determined. Six o-mannosyl residues and a 2-acetamido-2-deoxy-D-gIucosyl residue were released on digestion of a glyco-peptide in turn with a-o-mannosidase and -D-2-acetamido-2-deoxyglucosidase. The structure (5) was proposed on the basis of the results of enzymic hydrolysis, methylation, partial acetolysis, and Smith degradation. 

Amidine and Guanidine Derivatives. - The amidine analogue 103 of methyl 6-O-mannosyl-a-D-mannoside has been synthesized and is an effective inhibitor of a-mannosidase (Kj=2.6 Four (deoxy)monosaccharide AT-benzylamidine... 

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