title: Toward bioinspired galectin mimetics: identification of ligand-contacting peptides by proteolytic-excision mass spectrometry.
abstract: Clinically relevant bioactivities of human galectins (adhesion/growth-regulatory galactoside-specific lectins) inspired the design of peptides as new tools to elicit favorable effects (e.g., in growth control) or block harmful binding (e.g., in tissue invasion). To obtain the bioinspired lead compounds, we combined a proteolytic fragmentation approach without/with ligand contact (excision) with mass spectrometric identification of affinity-bound protein fragments, using galectin-1 and -3 as models. Two peptides from the carbohydrate recognition domains were obtained in each case in experimental series rigorously controlled for specificity, and the [157-162] peptide of galectin-3 proved to be active in blocking lectin binding to a neoglycoprotein and to tumor cell surfaces. This approach affords peptide sequences for structural optimization and intrafamily/phylogenetic galectin comparison at the binding-site level with a minimal requirement of protein quantity, and it is even amenable to mixtures.
authors.affiliation: Department of Chemistry, University of Konstanz, Konstanz, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Moise
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.forename: Frederike
authors.initials: F
authors.lastname: Eggers
authors.forename: Mickael
authors.initials: M
authors.lastname: Krzeminski
authors.forename: Michael
authors.initials: M
authors.lastname: Przybylski
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D032701:Biomimetics; D002417:Cattle; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D037161:Galectins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D007785:Lactose / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059748:Proteolysis; D012710:Serum Albumin, Bovine / Q000037:antagonists & inhibitors / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship
chemical_list: D037161:Galectins; D008024:Ligands; D010446:Peptide Fragments; D012710:Serum Albumin, Bovine; D007785:Lactose