title: Synthesis and evaluation of new thiodigalactoside-based chemical probes to label galectin-3.
abstract: New chemical probes were synthesized to label galectin-3. They are based on the high affinity thiodigalactoside ligand. The probes were synthesized with benzophenone or acetophenone moieties as the photolabel for covalent attachment to the protein. Besides labeling the protein, these aromatic photolabels also greatly enhance the affinity of the probes towards galectin-3, due to the interaction of the photolabel with two arginine guanidinium groups of the protein. The linkage between the sugar and the photolabel was varied as an ester, an amide, and a triazole. For the amide and triazole derivatives, a versatile synthetic route towards a symmetrical 3-azido-3-deoxy-thiodigalactoside was developed. The new probes were evaluated for their binding affinity of human galectin-3. They were subsequently tested for their labeling efficiency, as well as specificity in the presence of a protein mixture and a human cancer cell lysate.
authors.affiliation: Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NL.
authors.forename: Monique
authors.initials: M
authors.lastname: van Scherpenzeel
authors.forename: Ed E
authors.initials: EE
authors.lastname: Moret
authors.forename: Lluis
authors.initials: L
authors.lastname: Ballell
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
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: D001577:Benzophenones / Q000737:chemistry; D045744:Cell Line, Tumor; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D037502:Galectin 3 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D010777:Photochemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013194:Staining and Labeling; D013862:Thiogalactosides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001577:Benzophenones; D037502:Galectin 3; D008024:Ligands; D013862:Thiogalactosides; C047723:benzophenone; C031803:thiodigalactoside