Chemical Synthesis of Lipopolysaccharide Core
Genomic data and analytical studies of the past decade have revealed a multitude of novel structural features of the core region of the lipopolysaccharide of Gram-negative bacteria. The chapter presents an update of ongoing and recent synthetic efforts il
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Chemical Synthesis of Lipopolysaccharide Core Paul Kosma and Alla Zamyatina
5.1
Introduction
Genomic data and results compiled from analytical studies during the past decade have revealed a multitude of novel structural features within the core region of the lipopolysaccharide (LPS) of Gram-negative bacteria [1] (see also Chap. 2). Previous synthetic efforts have covered the basic structural units of the enterobacterial LPS core as well as biomedically relevant structures of O-antigens and capsular polysaccharides. These studies have already been summarized in close detail in the past decade. Hence this chapter will present an update of ongoing synthetic efforts using representative examples from the literature of the past decade [2–4]. The use of synthetic carbohydrate antigens as surrogates of the structures occurring in the core-region as well as repeating units of O-antigens and capsular polysaccharides serving as vaccine candidates has also been covered in excellent reviews [5, 6]. Synthetic approaches towards components of the inner core region have to deal with the elaboration of efficient protocols to prepare multigram amounts of the higher carbon aldoses L-glycero-D-manno-heptose and its 6-epimer as well as the octulosonic acids 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) and D-glyceroD-talo-oct-2-ulosonic acid (Ko) followed by transformation into suitable glycosyl donor and acceptor derivatives. Recent developments in the field with regard to these topics have therefore also been included in this review. Finally, the remarkable challenges associated with the need for orthogonal protecting groups and specific incorporation of additional groups such as phosphate, 2-aminoethyl phosphate or 4-deoxy-4-amino-L-arabinose substituents will also be discussed. Major research lines in the synthesis of core structures in the past few years covered truncated forms of LPS in order to elucidate their antigenic properties to be
P. Kosma (*) • A. Zamyatina Department of Chemistry, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria e-mail: [email protected]; [email protected] Y.A. Knirel and M.A. Valvano (eds.), Bacterial Lipopolysaccharides, DOI 10.1007/978-3-7091-0733-1_5, # Springer-Verlag/Wien 2011
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exploited as diagnostic markers and as lead structures for future vaccine development. Remarkable progress has been witnessed in defining the molecular basis for the interaction of Kdo-specific antibodies directed against synthetic antigens as well as oligosaccharides released and purified from bacterial LPS. Knowledge on the three-dimensional presentation of core oligosaccharides is still in its infancy and will undoubtedly benefit from the availability of defined synthetic products for structural studies by nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography to be complemented by molecular modeling approaches. In addition, these compounds may further be exploited as substrates for various enzymes acting in elongati
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