title: Tuning the preference of thiodigalactoside- and lactosamine-based ligands to galectin-3 over galectin-1.
abstract: Inhibitors for galectin-1 and -3 were synthesized from thiodigalactoside and lactosamine by derivatization of the galactose C3. Introduction of 4-phenyl-1H-1,2,3-triazol-1-yl substituents at the thiodigalactoside C3 by CuAAC, targeting arginine-arene interactions, increased the affinity to 13 nM but yielded little selectivity. The bulkier 4-(4-phenoxyphenyl)-1H-1,2,3-triazol-1-yl substituent, however, increased the preference for galectin-3 over galectin-1 to more than 200-fold. Modeling showed more arginine-arene interactions for galectin-3 than for galectin-1. Introducing 4-phenoxyaryl groups on lactosamine had a similar effect.
authors.affiliation: Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Hilde
authors.initials: H
authors.lastname: van Hattum
authors.forename: Hilbert M
authors.initials: HM
authors.lastname: Branderhorst
authors.forename: Ed E
authors.initials: EE
authors.lastname: Moret
authors.forename: Ulf J
authors.initials: UJ
authors.lastname: Nilsson
authors.forename: Hakon
authors.initials: H
authors.lastname: Leffler
authors.forename: Roland J
authors.initials: RJ
authors.lastname: Pieters
mesh_terms: D000606:Amino Sugars / Q000737:chemistry*; D037483:Galectin 1 / Q000737:chemistry*; D037502:Galectin 3 / Q000737:chemistry*; D008024:Ligands; D013058:Mass Spectrometry; D015394:Molecular Structure; D013862:Thiogalactosides / Q000737:chemistry*
chemical_list: D000606:Amino Sugars; D037483:Galectin 1; D037502:Galectin 3; D008024:Ligands; D013862:Thiogalactosides; C032233:lactosamine; C031803:thiodigalactoside