IbutionsConceived and designed the experiments: DPC MAM IW. Performed the experiments: DPC FJD. Analyzed the data: DPC FJD MAM IW. Contributed reagents/materials/analysis tools: IW. Wrote the paper: DPC MAM IW. Processing of images and performed statistical analyzes: FJD. Revised the manuscript: MAM. Accountable for pictures acquisition: IW.
Lipopolysaccharides (LPS) are amphiphilic glycolipids positioned in the outer leaflet of the cell membrane of Gram-negative bacteria, that are of high biomedical relevance as a result of their interaction with components on the innate and adaptive immune system of their respective hosts.[1] In structural terms, enterobacterial LPS displays a tripartite architecture comprising the endotoxically active diglucosamine unit (Lipid A) followed by a core region along with the Oantigenic polysaccharide chain.[2] 3-Deoxy–D-manno-oct-2-ulosonic acid (-Kdo) serves because the prevalent linkage sugar to Lipid A and constitutes the structurally conserved -Kdo(24)–Kdo disaccharide core domain. This simple Kdo unit is being extended by extra Kdo residues inside the LPS of Chlamydiaceae, a biomedically important obligate intracellular parasite.[3] The genus Chlamydia trachomatis is usually a leading cause of sexually transmitted illnesses, sooner or later resulting in infertility in ladies, but can also be accountable for conjunctivitis and secondary blindness.[4] The second genus harboring the species Chlamydophila psittaci and Chlamydophila pneumoniae is involved in pulmonary infections*[email protected]. Supporting data for this article is given by means of a hyperlink at the finish on the document.Pokorny and KosmaPageand the latter species has also been linked to chronic infections like arthritis and atherosclerosis.UBE2M, Human [5] All Chlamydiae share a truncated lipopolysaccharide wherein the Kdo component forms an immunodominant, family-specific trisaccharide epitope of the sequence Kdo-(28)–Kdo-(24)–Kdo.Insulin Protein Formulation [6] Also to this group-specific antigen, a second linear trisaccharide -Kdo-(24)–Kdo-(24)–Kdo and the branched tetrasaccharide Kdo-(24)[-Kdo-(28)]–Kdo-(24)–Kdo constitute further antigenic epitopes within the Chl.PMID:24458656 psittaci.[7] A similarly branched Kdo trisaccharide has also been identified inside the core area of Acinetobacter lwoffii F78 LPS.[8] Lately it has been shown, that these Kdo residues are involved in significant binding interactions with proteins, and insight in to the recognition of Kdo saccharides by monoclonal antibodies and Toll-like receptor-4 (TLR-4) has been accomplished in the molecular level.[9] Hence, the chemical synthesis of Kdo glycosides is an desirable objective within the field of (bio)organic chemistry so that you can deliver immunoreagents and antigens for the development of synthetic carbohydrate-based vaccines and diagnostics.[10] Glycosylation reactions of 3-deoxy-2-ulosonic acid donors are challenging because of the lack of a stereodirecting neighboring group at C-3, the deactivation of your anomeric center by the adjacent carboxyl group, the higher propensity of the glycosyl donors towards elimination reactions – top to glycal ester derivatives (e.g. three, Scheme 1) – and the acid sensitivity of your ketosidic linkage.[11] To improve stereoselectivity and coupling yields of glycoside formation, different approaches have already been reported which had been mostly primarily based on optimization of dedicated safeguarding and leaving groups. As a result, electron-donating (“arming”) safeguarding groups such as silyl ether, benzyl or isopropylidene groups have largely been used in o.