PLoS One 2013, 8, No

PLoS One 2013, 8, No. potentially life-threatening disease of the peripheral nervous system characterized by quick and progressive limb weakness. 1 The medical program and severity of GBS are variable, and approximately a quarter of the individuals develop respiratory failure or severe autonomic dysfunction.2,3 GBS often happens after a respiratory or gastrointestinal tract infection, and previous studies have shown some of these infections induce antibodies that cross-react with gangliosides at peripheral nerves thereby causing polyneuropathy.4 The type of infection and the specificity of the producing anti-ganglioside antibodies are important determinants of the subtype and clinical course of GBS.5 The most common pathogen causing the antecedent infection of GBS is (is a Gram-negative, non-spore-forming bacterium that is a common cause of gastroenteritis and is transmitted to humans through ingestion of insufficiently cooked poultry, contaminated milk, and water.10 It generates a lipo-oligosaccharide (LOS) that often terminates inside a structure resembling the saccharide moieties of gangliosides. In particular, LOSs of that are associated with GBS often create constructions mimicking the oligosaccharide moieties of GM1a and GD1a.11C13 In addition, strains have been isolated that express GD3, GM2, GM3, and GT1a mimics.14 Clinical and serologic data support a model in which the LOS of specific strains elicit antibodies that recognize both bacterial molecules and gangliosides, and acknowledgement of the second option biomolecules, which are abundantly indicated in the nervous system where they are involved in neurotransmission, causes neurological disfunction.11,15 Anti-GM1a antibodies are the most frequently observed antibodies in GBS and associated with a severe and real motor clinical phenotype.16,17 Although there is strong scientific support for the involvement of anti-ganglioside antibodies in the pathogenesis of GBS,2 molecular mechanisms by which immunotolerance para-Nitroblebbistatin is broken leading to autoimmune-like responses are not well understood. Furthermore, the part of anti-ganglioside antibodies in analysis VPS33B is definitely fraught with troubles, and in particular the rate of recurrence and specificity of anti-ganglioside antibodies are low leading to false bad results. The positive predictive value of anti-ganglioside antibodies, especially those of the IgM class, is also compromised because these can occur in other diseases. Detection of anti-ganglioside antibodies is mainly performed by ELISA using gangliosides, 18 usually obtained by isolation from natural sources. These compounds are often not homogeneous, and only para-Nitroblebbistatin a limited number of structures are readily para-Nitroblebbistatin available, which is usually impeding comprehensive analysis of structureCbinding associations and mechanisms by which they promote nerve damage. During natural infections, the immune system is usually primed by LOS of strains,19 and thus we hypothesized that anti-ganglioside antibodies elicited during contamination are directed to epitopes that straddle the inner core region of LOS and the ganglioside structural analogs. To test this mode of immune recognition, we synthesized a large panel of oligosaccharides composed of the inner core oligosaccharide of the LOS of extended by various ganglioside mimics. Compound 1 resembles the inner core oligosaccharide of core oligosaccharides and normal ganglio-oligosaccharide library by a chemoenzymatic approach: (A) synthetic ganglioside mimic and ganglioside oligosaccharide library; (B) chemically synthesized inner core hexasaccharide 1 and enzymatic extension of 1 1 to afford compounds such para-Nitroblebbistatin as GT1a ganglioside mimic 6. RESULTS AND DISCUSSION Chemical Synthesis of Inner Core Oligosaccharide (1). The chemical synthesis of the inner core hexasaccharide 1 is usually challenging due to the low acceptor reactivity of the C5-hydroxyl of Kdo-= 5.26 ppm), which was common for an and have been identified that can assemble ganglio-series oligosaccharides. These include the that can form GM3; the which can synthesize GM2; that can prepare GM1; and the bifunctional sialyltransferase CstII41 from that has both = 1.580) of terminal = 4.016) of para-Nitroblebbistatin and were not able to cleave the internal and branched Neu5Ac moiety. Gratifyingly, could remove the Neu5Ac residue of 4 to give GA1 mimic 11. A relatively high concentration of this neuraminidase and a prolonged incubation time were required to cleave the internal Neu5Ac residue. Sialylation of 11 using PmST1 and CMP-Neu5Ac afforded GM1b mimic 12, which could be further sialylated using CstII to provide GD1c mimic 13 (Scheme 2C). The corresponding ganglioside oligosaccharides 14C25 (Physique S11) were prepared by a similar strategy starting from lactose altered by an anomeric aminopropyl linker. The preparation of GA1, GM1b, and GD1c did not require expensive contamination, and the results were compared to healthy control serum samples. For this purpose,.

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