Synthesis of O-galactosyl aldoximes as potent LacNAc-mimetic galectin-3 inhibitors

A panel of anomeric oxime ether derivatives of β-galactose were synthesized via the reaction of O-β-d-galactopyranosylhydroxylamine with aldehydes. The oxime ethers were evaluated as inhibitors against galectin-3 in a competitive fluorescence polarization assay. The best inhibitor, [E]-O-(β-d-galactopyranosyl)-indole-3-carbaldoxime (E-52), had a Kd value of 180 μM, which is 24 times better than methyl β-d-galactopyranoside (Kd = 4400 μM) and in the same range as methyl lactoside (Kd = 220 μM).