172146-98-4Relevant academic research and scientific papers
Novel mimics of sialyl Lewis X: Design, synthesis and biological activity of a series of 2- and 3-malonate substituted galactoconjugates
Marinier, Anne,Martel, Alain,Bachand, Carol,Plamondon, Serge,Turmel, Brigitte,Daris, Jean-Paul,Banville, Jacques,Lapointe, Philippe,Ouellet, Carl,Dextraze, Pierre,Menard, Marcel,Wright, John J.K,Alford, Julie,Lee, Debbie,Stanley, Paul,Nair, Xina,Todderud, Gordon,Tramposch, Kenneth M
, p. 1395 - 1427 (2007/10/03)
A series of potent inhibitors of P-selectin as potential antiinflammatory agents is reported. These compounds are derivatives of galactocerebrosides bearing a malonate side chain in positions 2 and 3 of the galactose moiety. Based on the binding mode of sialyl Lewis X, the two acidic groups of the malonate are designed to form ionic interactions with two important lysines in the active site of P-selectin, Lys113 and Lys111. On the other hand the 4- and 6-hydroxy groups on the galactosering are arranged to chelate the calcium ion in the P-selectin active site. The synthesis and the biological activity of this series of compounds are described. Lead compounds having a greater potency than sialyl lewis X are identified. Copyright
Synthesis of three tethered trisaccharides to probe entropy contributions in carbohydrate-protein interactions
Zhang, Ping,Bundle, David R.
, p. 189 - 208 (2007/10/03)
Crystal structure data show that the branched trisaccharide 1 constitutes the complete antigenic determinant of the Salmonella serogroup B antigen that is recognized by monoclonal antibody SE155.4. In an effort to characterize the entropic costs associated with immobilization of glycosidic torsional angles in the bound state, three distinct intramolecularly tethered analogues of this trisaccharide 2-4 have been synthesized. Two trisaccharides are tethered by a methylene acetal via the O-2 position of the 3,6-dideoxy-hexose, abequose to either O-2 of galactose (2) or O-4 of mannose (3). The third tether, α,α'-di-thio-p-xylene, spans the C-6 atoms of the mannose and galactose residues to create trisaccharide 4. The acetal tethers of 2 and 3 span hydroxyl centers that are known to be involved in intramolecular sugar-sugar hydrogens bonds, but both trisaccharides are biologically inactive due to distorted conformations that cannot be accommodated in the antibody binding site. Trisaccharide 4 is active since both hydroxymethyl groups of galactose and mannose are solvent exposed in the bound state and the constrained conformation of 4 is virtually superimposable on the bound conformation of 1. Despite the retained complimentary and significant reduction of torsional flexibility, trisaccharide 4 exhibits a ΔG° = -7.6 kcal mol-1 compared to ΔG° = -7.1 kcal mol-1 for 1. The modest free energy gain for the tethered trisaccharide 4 arises from a small entropy gain (TΔΔS = 0.3 kcal mol-1) and an even smaller enthalpic change (ΔΔH = -0.2 kcal mol-1).
