Synthesis of O-galactosyl aldoximes as potent LacNAc-mimetic galectin-3 inhibitors.
A panel of anomeric oxime ether derivatives of beta-galactose were synthesized via the reaction of O-beta-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-(beta-D-galactopyranosyl)-indole-3-carbaldoxime (E-52), had a Kd value of 180 microM, which is 24 times better than methyl beta-D-galactopyranoside (Kd=4400 microM) and in the same range as methyl lactoside (Kd=220 microM).
Tejler
Johan
J
Organic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden.
Leffler
Hakon
H
Nilsson
Ulf J
UJ
D015195:Drug Design; D005690:Galactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D037502:Galectin 3 / Q000037:antagonists & inhibitors*; D007536:Isomerism; D007700:Kinetics; D008968:Molecular Conformation; D015394:Molecular Structure; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D037502:Galectin 3; D010091:Oximes; D005690:Galactose