Glycomimetic Glycoconjugates as Lectin Antagonists

Interference with oligosaccharide-mediated recognition events can be achieved using functional mimics of carbohydrates, that could thus be used to modulate / alter signal transmission, or to prevent the onset of diseases. In recent years our laboratory has designed and prepared glycomimetic ligands of well-known target lectins1 (cholera toxin,1,2 DC-SIGN,1,3 MBL, PA-IIL4). More recently, we have concentrated our attention on -glycosyl amides as mimics of glycosides potentially endowed with metabolic stability properties3c-d,4,5 or mimicking natural glycopeptides.6 All the mimics we are preparing share some common features relative to the natural oligosaccharide counterpart : reduction of the structural and/or synthetic complexity, structural similarity to the pharmacophoric fragment/epitope, chemical and enzymatic stabilization. Additionally, most of these ligands include appropriate tethers, designed to allow synthesis of (pseudo)glycoconjugates,1, 3a-b, 7 or conjugation to solid surfaces. The presentation will discuss the synthetic methodologies developed to synthesize these molecules, as well as some of the applications we are exploring.