C-Disaccharides as Probes for Carbohydrate Recognition - Investigation of the Conformational Requirements for Binding of Disaccharide Mimetics of Sialyl Lewis X

A set of C‐disaccharide analogs was designed to probe the recognition of a known O‐disaccharide mimetic of sialyl Lewis X, to P‐selectin. The synthesis of the C‐glycosides centered on the de novo construction of the galactose residue via an oxocarbenium ion/enol ether cyclization. Conformational analysis was performed by a combination of NMR spectroscopy and molecular mechanics (MM) and molecular dynamics (MD) calculations. The inhibition of P‐selectin binding was evaluated in a P‐selectin Biacore assay. At 12 mM, the O‐glycoside showed 48 % inhibition of binding, while the C‐glycoside analogs exhibited between 25–31 % inhibition. This data is discussed within the context of the active conformation of sLex and the conformational behavior of these ligands. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)