title: Synthesis of multivalent lactose derivatives by 1,3-dipolar cycloadditions: selective galectin-1 inhibition.
abstract: Acetylene derivatives of phenylalanine, phenethylamine and the multifunctional unnatural amino acids, phenyl-bis-alanine and phenyl-tris-alanine, were synthesized and functionalized with 2-azidoethyl beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranoside via regioselective copper(I)-mediated 1,3-dipolar cycloaddition to give a panel of mono-, di- and trivalent lactoside derivatives. Evaluation of the compounds as inhibitors against the tumour- and inflammation-related galectin-1, -3, -4N, -4C, -4, -7, -8N and -9N revealed a divalent compound with a Kd value as low as 3.2 microM for galectin-1, which corresponded to a relative potency of 30 per lactose unit as compared to the natural disaccharide ligand lactose. This divalent compound had at least one order of magnitude higher affinity for galectin-1 than for any of the other galectins investigated.
authors.affiliation: Organic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Tejler
authors.forename: Erik
authors.initials: E
authors.lastname: Tullberg
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Frejd
authors.forename: Hakon
authors.initials: H
authors.lastname: Leffler
authors.forename: Ulf J
authors.initials: UJ
authors.lastname: Nilsson
mesh_terms: D000114:Acetylene / Q000031:analogs & derivatives / Q000138:chemical synthesis; D037483:Galectin 1 / Q000037:antagonists & inhibitors*; D007785:Lactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D014230:Triazoles / Q000138:chemical synthesis
chemical_list: D037483:Galectin 1; D014230:Triazoles; D007785:Lactose; D000114:Acetylene