Lipopolysaccharides (LPSs) and lipooligosaccharides (LOSs) are important surface antigens for a wide variety of gram-negative bacteria. LPS and LOS consist of a lipid A and a polysaccharide (PS) or an oligosaccharide (OS). The core OS moiety of LPS and LOS consists of a structurally variable region and a conserved inner-core OS. 3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) is a component of the inner-core OS. Recently, human IgG2 antibodies, which were isolated by using 15253 LOS from serum-resistant gonococcal strain 15253 as an affinity ligand, recognized the 3,4-branched and 2,3:3,4-dibranched neisserial LOSs and Salmonella minnesota Rb and Re mutant LPSs [1]. To understand these epitopes, we are synthesizing Kdo containing oligosaccharides of various sizes. We have reported the syntheses of dimeric Kdo, Kdo(α2-4)Kdo and Kdo(α2-8)Kdo from a common Kdo intermediate [2]. In this presentation, we will describe the synthesis of biotin conjugates of inner-core oligosaccharides of LPS/LOS.
Kdo containing oligosaccharides 1-4 were prepared by reported procedure. Isopropyliden, Benzoyl, and methyl ester group were hydrolyzed by the treatment with aqueous trifluoroacetic acid, followed with 0.1 M sodium hydroxide in moderate to good yield. The deprotected allyl glycosides was attached with methyl thioglycolate under UV irradiation and resulted methyl esters was converted into hydrazine amide 5 (48-89%). Coupling of the spacer compounds with Biotin-sulfo-OSu afforded the corresponding biotin-OS conjugates 6.
[1] Ichiyanagi, T. et al. Tetrahedron, 2011, 67, 5964-5971. [2] Yamasaki, R. et al. Infect. Immun. 2010, 3247-3257.
