Attachment of 4-amino-4-deoxy-L-arabinose (Ara4N) to phosphates or sugar hydroxyl groups of lipopolysaccharide (LPS) contributes to bacterial resistance against common antibiotics. For a detailed study of antigenic properties and binding interactions, Ara4N-containing inner-core ligands related to Burkholderia and Proteus LPS have been synthesized in good yields. Glycosylation at position 8 of allyl glycosides of oct-2-ulosonic acids (Ko, Kdo) has been accomplished using an N-phenyltrifluoroacetimidate 4-azido-4-deoxy-L-arabinosyl glycosyl donor followed by azide reduction and global deprotection. The β-L-Ara4N-(1 → 8)-α-Kdo disaccharide was further extended into the branched β-L-Ara4N-(1 → 8)[α-Kdo-(2 → 4)]-α-Kdo trisaccharide via a regioselective glycosylation of a protected triol intermediate. Synthesis of Ara4N-modified lipid A part structure occurring in the LPS of Burkholderia, Pseudomonas, and Klebsiellla strains was accomplished using the H-phosphonate approach. The stereocontrolled assembly of the phosphodiester linkage connecting glycosidic centers of two aminosugars was elaborated employing an anomeric H-phosphonate of cyclic silyl-ether protected 4-azido-4-deoxy-β-L-arabinose, which was coupled to the hemiacetal of the lipid A GlcN-disaccharide backbone. Conditions for global deprotection, which warrant the integrity of “double anomeric” phosphodiester linkage, were successfully developed. Introduction of thiol-terminated spacer at the synthetic ligands allows both coupling to bovine serum albumin (BSA) and immobilization on gold nanoparticles as well as generation of glycoarrays.
Conference
European Carbohydrate Symposium (Eurocarb-16), 16th, Sorrento, Italy, 2011-07-03–2011-07-07
References
1 10.1126/science.321.5887.356, G. Taubes. Science321, 356 (2008).Search in Google Scholar PubMed
2 10.1002/anie.200600350, F. von Nussbaum, M. Brands, B. Hinzen, S. Weigand, D. Häbich. Angew. Chem., Int. Ed.45, 5072 (2006).Search in Google Scholar PubMed
3 10.1128/IAI.00212-10, S. A. Loutet, M. A. Valvano. Infect. Immun.78, 4088 (2010).Search in Google Scholar PubMed PubMed Central
4 10.1128/CMR.00058-07, A. Y. Peleg, H. Seifert, D. L. Paterson. Clin. Microbiol. Rev.21, 538 (2008).Search in Google Scholar PubMed PubMed Central
5 10.1016/j.molmed.2007.04.004, G. D. Wright, A. D. Sutherland. Trends Mol. Med.133, 260 (2007).Search in Google Scholar PubMed
6 10.1146/annurev.biochem.71.110601.135414, C. Raetz, C. Whitfield. Annu. Rev. Biochem.71, 635 (2002).Search in Google Scholar PubMed PubMed Central
7 O. Holst, A. Molinaro. In Microbial Glycobiology, A. P. Moran, O. Holst, P. J. Brennan, M. von Itzstein (Eds.), Chap. 3, pp. 29–55, Elsevier, Amsterdam (2009).10.1016/B978-0-12-374546-0.00003-1Search in Google Scholar
8 10.1177/1753425909347400, T. Ierano, P. Cescutti, M. R. Leone, A. Luciani, R. Rizzo, V. Raia, R. Lanzetta, M. Parrilli, L. Maiuri, A. Silipo, A. Molinaro. Innate Immun.16, 354 (2010).Search in Google Scholar PubMed
9 10.1111/j.1365-2958.2006.05519.x, P. J. Brett, M. N Burtnick, D. S. Snyder, J. G. Shannon, P. Azadi, F. C. Gherardini. Mol. Microbiol.63, 379 (2007).Search in Google Scholar PubMed PubMed Central
10 10.1002/chem.200601406, A. Silipo, A. Molinaro, T. Ieranò, A. De Soyza, L. Sturiale, D. Garozzo, C. Aldridge, P. A. Corris, C. M. A. Khan, R. Lanzetta. Chem.—Eur. J.13, 3501 (2007).Search in Google Scholar PubMed
11 10.1164/rccm.200304-592OC, A. De Soyza, C. D. Ellis, C. M. A. Khan, P. A. Corris, R. D. de Hormaeche. Am. J. Respir. Crit. Care Med.170, 70 (2004).Search in Google Scholar
12 10.1016/S0008-6215(02)00037-X, E. Vinogradov, Z. Sidorczyk, Y. A. Knirel. Carbohydr. Res.337, 835 (2002).Search in Google Scholar
13 10.1002/ejoc.200600520, A. Silipo, A. Molinaro, D. Comegna, L. Sturiale, P. Cescutti, D. Garozzo, R. Lanzetta, M. Parrilli. Eur. J. Org. Chem. 4874 (2006).Search in Google Scholar
14 10.1128/AAC.45.7.2030-2037.2001, A. J. McCoy, H. Liu, T. J. Falla, J. S. Gunn. Antimicrob. Agents Chemother.45, 2030 (2001).Search in Google Scholar
15 10.1016/S0161-5890(03)00162-7, D. A. Devine. Mol. Immun.40, 431 (2003).Search in Google Scholar
16 10.1093/jac/dkm357, A. P. Zavascki, L. Z. Goldani, J. Li, R. L. Nation. J. Antimicrob. Chemother.60, 1206 (2007).Search in Google Scholar
17 10.1016/0008-6215(88)84118-1, J. J. Naleway, C. H. R. Raetz, L. Anderson. Carbohydr. Res.179, 199 (1988).Search in Google Scholar
18 B. Müller, M. Blaukopf, A. Hofinger, A. Zamyatina, H. Brade, P. Kosma. Synthesis 3143 (2010).10.1055/s-0030-1258174Search in Google Scholar
19 10.1016/j.tet.2006.01.084, N. Oka, M. Shimizu, K. Saigo, T. Wada. Tetrahedron62, 3667 (2006).Search in Google Scholar
20 10.1016/S0040-4039(00)84611-0, J. E. Marugg, M. Tromp, E. Kuyl-Yeheskiely, G. A. van der Marel, J. H. van Boom. Tetrahedron Lett.27, 2661 (1986).Search in Google Scholar
21 10.1021/ja9726015, T. Wada, Y. Sato, F. Honda, S. Kawahara, M. Sekine. J. Am. Chem. Soc.119, 12710 (1997).Search in Google Scholar
22 10.1081/NCN-120018619, S. Sigurdsson, R. Strömberg. Nucleosides, Nucleotides Nucleic Acids22, 1 (2003).Search in Google Scholar
23 10.1016/S0008-6215(98)00179-7, A. Isshiki, K. Kawahara, U. Zähringer. Carbohydr. Res.313, 21 (1998).Search in Google Scholar
24 A. D. Vinion-Dubiel, J. B. Goldberg. J. Endotoxin Res.9, 201 (2003).Search in Google Scholar
25 10.1002/chem.200600186, E. Vinogradov, B. Lindner, G. Seltmann, J. Radziejewska-Lebrecht, O. Holst. Chem.—Eur. J.12, 6692 (2006).Search in Google Scholar
26 10.1016/0008-6215(93)87007-F, P. Kosma, M. Strobl, L. März, S. Kusumoto, K. Fukase, L. Brade, H. Brade. Carbohydr. Res.283, 93 (1993).Search in Google Scholar
27 10.1081/SCC-120026311, P. Rajakumar, V. Murali. Synth. Commun.33, 3891 (2003).Search in Google Scholar
28 10.1046/j.1432-1327.2000.01001.x, E. Vinogradov, J. Radziejewska-Lebrecht, W. Kaca. Eur. J. Biochem.267, 262 (2000).Search in Google Scholar PubMed
29 10.1002/ejoc.201101171, M. Blaukopf, B. Müller, A. Hofinger, P. Kosma. Eur. J. Org. Chem. (2011). In pressSearch in Google Scholar PubMed PubMed Central
© 2013 Walter de Gruyter GmbH, Berlin/Boston
