Synthesis and affinity evaluation of a small library of bidentate cholera toxin ligands: towards nonhydrolyzable ganglioside mimics.
A small library of nonhydrolyzable mimics of GM1 ganglioside, featuring galactose and sialic acid as pharmacophoric carbohydrate residues, was synthesized and tested. All compounds were synthesized from readily available precursors using high-performance reactions, including click chemistry protocols, and avoiding O-glycosidic bonds. Some of the most active molecules also feature a point of further derivatization that can be used for conjugation with polyvalent aglycons. Their affinity towards cholera toxin was assessed by weak affinity chromatography, which allowed a systematic evaluation and selection of the best candidates. Affinity could be enhanced up to one or two orders of magnitude over the affinity of the individual pharmacophoric sugar residues.
Cheshev
Pavel
P
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano via Venezian 21, 20133 Milano, Italy.
Morelli
Laura
L
Marchesi
Marco
M
Podlipnik
Crtomir
C
Bergström
Maria
M
Bernardi
Anna
A
D002772:Cholera Toxin / Q000138:chemical synthesis* / Q000737:chemistry; D005677:G(M1) Ganglioside / Q000737:chemistry*; D005732:Gangliosides / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008024:Ligands
D005732:Gangliosides; D008024:Ligands; D005677:G(M1) Ganglioside; D002772:Cholera Toxin