title: Inhibition of galectins with small molecules.
abstract: Evidence that the galectin family of proteins plays crucial roles in cancer, inflammation, and immunity has accumulated over the last decade. The galectins have consequently emerged as interesting drug targets. A majority of galectin functions occurs by means of cross-linking glycoproteins and by doing so controlling glycoprotein cellular localization and residence times. The glycoprotein cross-linking occurs when galectin dimers or multimers, or galectins with two binding sites, bind galactose-containing glycans of the glycoproteins. Such galectin-glycan interactions have been successfully blocked with compounds having multivalent presentation of galactose, lactose, or N-acetyllactosamine, with peptides, and with small carbohydrate (galactose) derivatives. This review summarizes and analyzes attempts to develop efficient and selective small-molecule galectin inhibitors through derivatization of monosaccharides, mainly galactosides, with non-carbohydrate structures that protrude into subsites adjacent to the core-conserved galactose-recognizing site of the galectins.
authors.affiliation: Organic Chemistry, Lund University POB 124, SE-221 00 Lund, Sweden.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Oberg
authors.forename: Hakon
authors.initials: H
authors.lastname: Leffler
authors.forename: Ulf J
authors.initials: UJ
authors.lastname: Nilsson
mesh_terms: D015195:Drug Design; D005697:Galactosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D037161:Galectins / Q000037:antagonists & inhibitors*; D008970:Molecular Weight; D009005:Monosaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D005697:Galactosides; D037161:Galectins; D009005:Monosaccharides