Discovery of galectin ligands in fully randomized combinatorial one-bead-one-compound (glyco)peptide libraries

Human lectins (galectins) are emerging targets for drug design. Combinatorial one-bead-one-compound (glyco)peptide libraries were screened with galectin-1 and -3. Testing lead (glyco)peptides includes medically relevant inhibition assays with tumour cells. The involvement of human lectins (galectins) in disease progression accounts for the interest to design potent inhibitors. Three fully randomized hexa(glyco)peptide libraries were prepared using the portion mixing method combined with ladder synthesis. On-bead screening with fluorescently labelled galectin-1 and -3 yielded a series of lead structures, whose inhibitory activity on carbohydrate-dependent galectin binding was tested in solution by solid-phase and cell assays. The various data obtained define the library approach as a facile route for the discovery of selective (glyco)peptide-based galectin inhibitors.