Disease relevance of D-ManN

• In vivo, mAb 13D9 effectively controlled metastasis of leukemic cells RMA when mice were administered the precursor N-propionylated mannosamine [1].
• The cell walls of Staphylococcus aureus H were found to contain mannosamine in an amount (28.1 nmol/mg) comparable to the content of muramic acid 6-phosphate [2].
• N-Propionyl, N-butyryl (N-Bu), and N-benzoyl mannosamine, as precursors of sialic acid biosynthesis, were incubated with human melanoma SK-MEL-28 cells and resulted in the replacement of N-acetyl groups on the cell surface sialic acid residues, including those associated with GD3 [3].
• A selection strategy was devised to screen a Mycobacterium tuberculosis genomic library in Mycobacterium smegmatis for clones conferring conditional resistance to ManN, with the rationale that overexpression of the gene(s) encoding a target of ManN would impart a ManN-resistant phenotype under these conditions [4].
• Given hexosaminidases' important roles in osteoarthritis, we developed two straightforward and efficient syntheses of C1 nitrogen iminocyclitols from two readily available starting materials, D-mannosamine hydrochloride and the microbial oxidation product of fructose [5].

High impact information on D-ManN

• Moreover, complete inhibition of GPI biogenesis by mannosamine treatment did not impair the HBsAg apical secretion, discarding the possibility that HBsAg could be "hitchhiking" with a newly synthesized GPI-protein [6].
• The leukemic T-cell lines, subgrouped according to the degree of mannosamine inhibition on nucleic acid biosyntheses, were: Subgroup 1, HPB-MLT cells; Subgroup 2, CCRF-HSB-2 and HPB-ALL cells; and Subgroup 3, MOLT-4 cells [7].
• We observed heterogeneity of mannosamine susceptibility among those cell lines [7].
• Thus, the primary target of the tumoricidal activity of mannosamine may also be the cellular membranes [7].
• Morphological and pulse-chase studies with isolated pancreatic lobules revealed that after inhibition of GPI-anchor biosynthesis by mannosamine or the fungal metabolite YW 3548, granule formation was impaired leading to an accumulation of newly synthesized proteins in the Golgi apparatus and the rough endoplasmic reticulum [8].

Biological context of D-ManN

• On the basis of these results, it is concluded that aminosugars, especially ManN, produce H2O2 to cause DNA damage, which mediates apoptosis resulting in tumor growth inhibition [9].
• These results suggest that ManN-induced apoptosis is preceded by H2O2-mediated DNA damage [9].
• They are, therefore, released with neuraminidases or by mild acid hydrolysis and then converted with neuraminic acid aldolase to their corresponding mannosamine derivatives, which are then PMP-labeled, separated, and quantitated as described above [10].
• Mannosamine inhibits GPtdIns biosynthesis at a concentration of 5 mm, but neither an accumulation of aberrant intermediates nor significant inhibition of total protein biosynthesis was observed in the presence of this analogue [11].
• These results suggest that the suppression of NK activity by amino sugars is due to the reduction of the ATP-based energy supply of the effector cells and that amino sugars, especially D-mannosamine, should be recognized as potent suppressors of natural cell-mediated immunity [12].

Anatomical context of D-ManN

• Pre-incubation of cells in 10 mM D-mannosamine, an inhibitor of GPI incorporation into protein, resulted in a reduction of the incorporation of label into the three GPI-anchored proteins, nearly complete inhibition of differentiation and a reduction in the rate of digestive vacuole formation [13].
• Aprotinin, a plasmin inhibitor, and mannosamine, which inhibits the synthesis of glycosylphosphatidylinositol (GPI), thereby preventing anchorage of GPI-linked proteins such as uPAR to the cell membrane, also decreased IGF-II- (P<0.05 for both) but not IGF-I-induced migration [14].
• This effect of mannosamine appears to be due to its capacity to inhibit the synthesis of glycosylphosphatidylinositol (GPI)-linked proteins by chondrocytes since the GPI synthesis inhibitor 2-deoxyfluoroglucose (2-DFG) also inhibited the aggrecanase response to IL-1b and RA in rat cells [15].
• Mannosamine inhibits aggrecanase-mediated changes in the physical properties and biochemical composition of articular cartilage [16].
• In control rats, binding of epididymal spermatozoa to Vicia faba, a lectin specific for glucose and glucosamine, and mannose and mannosamine residues, decreased from the proximal caput to the distal corpus coincident with the increase in alpha-glucosidase activity on the epithelial brush border [17].

Associations of D-ManN with other chemical compounds

• In this report we show that mannosamine effectively inhibits the biosynthesis of both free glycosylated inositol phospholipids and the lipophosphoglycans of Leishmania mexicana [18].
• The acidic polymer fraction obtained by heating the cell walls at pH 2.5 was shown to contain mannosamine and glycerol in addition to the components of ribitol teichoic acid [2].
• Two sugars, glucosamine and mannosamine, prevented the disappearance of vacuoles [19].
• Like natural CL-43, the recombinant is secreted as trimeric forms that show a preference for mannose and N-acetyl mannosamine [20].
• The N-acetyl-beta-glucosaminidase activities of both isoenzymes are strongly inhibited, in decreasing order, by N-acetyl-galactosamine, mannosamine, disaccharic acid lactone, N-acetylglucosamine and gluconolactone [21].

Gene context of D-ManN

• Mannosamine treatment, which down-regulates cell-surface uPAR, decreased MEF-2 migration by 40% without significantly affecting MEF-1 migration [22].
• Recent studies have demonstrated that the hexosamines glucosamine (GlcN) and mannosamine (ManN) can inhibit aggrecanase-mediated cleavage of aggrecan in IL-1-treated cartilage cultures [16].
• The inhibition of glycosylphosphatidylinositol anchor biosynthesis by mannosamine has been described previously in the procyclic forms of Trypanosoma brucei and in mammalian cells (Lisanti, M. P., Field, M. C., Caras, I. W. J., Menon, A. K., and Rodriguez-Boulan, E. (1991) EMBO J. 10, 1969-1977) [23].
• The biosynthesis of lipoarabinomannan (LAM), a key mycobacterial lipoglycan that has been implicated in numerous immunoregulatory functions, was examined utilizing D-mannosamine (ManN) as a tool to identify mannosyltransferase genes involved in LAM synthesis [4].
• THe beta-galactoside-binding lectin binds to glucosamine, mannosamine and galactosamine in addition to beta-galactoside, as determined by the inhibition of haemagglutination [24].

Analytical, diagnostic and therapeutic context of D-ManN

• Formation of unusual mannosamine-containing lipid-linked oligosaccharides in Madin-Darby canine kidney cell cultures [25].
• The soluble enzyme was purified nearly 500-fold with 9-12% recovery to a state approaching homogeneity using: (1) (NH4)2SO4 precipitation; (2) affinity chromatography on immobilized mannan and D-mannosamine; (3) ion-exchange (DE-52) column chromatography; (4) molecular-sieve chromatography [26].
• Further, paper chromatography of the enzymatic digestion products of the binding factors reveals that N-acetylgalactosamine residues are released from the retina factor while mannosamine residues are released from the cerebral lobe factor [27].
• Flow cytometry showed that ManN enhanced the production of intracellular peroxides [9].
• Pulsed-field gel electrophoresis showed that ManN caused cellular DNA cleavage at a lower concentration than those causing apoptosis [9].

References