title: Screening for galectin-3 inhibitors from synthetic lacto-N-biose libraries using microscale affinity chromatography coupled to mass spectrometry.
abstract: The synthesis and screening of two beta-D-Galp-(1-3)-beta-d-GlcpN (lacto-N-biose) disaccharide libraries are reported. Solution-phase synthetic modifications at the HO-2' and NH positions were performed in an effort to enhance the affinity toward galectin-3, a galactose-binding protein involved in tumor metastasis, apoptosis, and inflammation. The libraries were screened for galectin-3 binding by microscale frontal affinity chromatography coupled to mass spectrometry (FAC/MS) allowing for rapid ranking of the different inhibitors and the determination of the galectin-3 binding Kd's. Compounds bearing a hydrophobic substituent on the NH group showed the highest affinity for the lectin. The N-naphthoyl derivative (Kd = 10.6 microM) was the best inhibitor with a 7 times increased affinity as compared to the N-acetyl parent compound (Kd = 73.3 microM).
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada. sebastien.fort@cermav.cnrs.fr
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fort
authors.forename: Hyo-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Ole
authors.initials: O
authors.lastname: Hindsgaul
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D002846:Chromatography, Affinity; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D037502:Galectin 3 / Q000037:antagonists & inhibitors*; D008024:Ligands; D013058:Mass Spectrometry; D015394:Molecular Structure; D011485:Protein Binding
chemical_list: D004187:Disaccharides; D037502:Galectin 3; D008024:Ligands; C033398:galactosyl-1,3-N-acetylglucosamine; D000117:Acetylglucosamine