SYNTHESIS OF “HIGH-MANNOSE” OLIGOSACCHARIDE MIMICS – AFFINITY CONSTANTS TOWARD CONCANAVALIN A

« High-mannose » type N-glycans are well known to participate in quality control and intracellular traffic of glycoproteins. They cover the surface of many pathogenic microorganisms and are the targets of the immune system cells through their mannose receptors.

Several groups have reported the synthesis of such complex structures but it remains very cumbersome and costly. Their uses as carbohydrates-based vaccines^[1] and as recognition moieties in drug delivery^[2] or in antigen targeting to dendritic cells^[3] have also been investigated.

In the pursuing of our work to investigate the recognition phenomena of “high-mannose” type oligosaccharides with lectins,^[4] we undertook to design “high-mannose” mimics that retain as much as possible the three-dimensional structure of the native molecule. The synthesis of octa^[5] and nona-oligomannosides mimics by replacing three mannose units with triazoles using "click chemistry" will be presented and discussed as well. The efficiency of the Man₈ mimic to inhibit concanavalin A binding to yeast mannan (IC₅₀ = 12 µM) will be compared to its natural analogues (IC₅₀ = 5, 17µM for Man₈ and Man_7, respectively). Preliminary results of Concanavalin A / Mimics recognition studies based on Mass spectrometry (ESI-MS) will also be presented.