Inhibitory potential of chemical substitutions at bioinspired sites of β-d-galactopyranose on neoglycoprotein/cell surface binding of two classes of medically relevant lectins

摘要: Galactose is the key contact site for plant AB-toxins and human adhesion/growth-regulatory galec-tins. Natural anomeric extensions 3 0-substitutions enhance its reactivity, thus prompting us to test potential of respective chemical substitutions galactose in quest develop potent inhibitors. Biochemical screening a glycoside library with 60 substances solid-phase assay was followed by examining compounds' activity protect cells from lectin binding. By testing 32 extensions, 18 compounds additional 0-substitution, three lactosides two Lewis-type trisaccha-rides rather mild effects compared common haptenic inhibitor lactose were detected both assays. When using trivalent glycoclusters marked enhancements 6-to 8-fold increases revealed toxin four tested galectins. Since most compound also 0-substituted thiogalactosides reduced cell growth tumor line at millimolar concentrations, biocompatible scaffolds will be required further developments. The synthesis suitable glycoclusters, presenting headgroups which exploit differences ligand selection interlectin comparison reduce cross-reactivity, documented strategic combination initial biochemical assays are considered instrumental advance design.