title: Assessing the inhibitory potency of galectin ligands identified from combinatorial (glyco)peptide libraries using surface plasmon resonance spectroscopy.
abstract: Combinatorial (glyco)peptide libraries offer the possibility to define effective inhibitors of protein (lectin)-glycan interactions. If a (glyco)peptide surpasses the inhibitory potency of the free sugar, then the new peptide-lectin contacts underlying the affinity enhancement may guide further rational drug design. Focusing on the adhesion/growth regulatory human galectins 1 and 3, a screening of three combinatorial solid-phase (glyco)peptide libraries, containing Gal(beta1-O)Thr, Gal(beta1-S)Cys/Gal(beta1-N)Asn, and Lac(beta1-O)Thr, with the fluorescently labeled lectins had led to a series of lead compounds. To define the inhibitory potency of a selection of resynthesized (glyco)peptides systematically, a surface plasmon resonance-based inhibition assay with immobilized asialofetuin was set up. (Glyco)Peptides with up to 66-fold potency relative to free lactose as inhibitor were characterized. The presence of lactose in the most effective glycopeptides indicated the presence of affinity-enhancing peptide-lectin contacts. In addition to drug design, they may be helpful for fine-structural analysis of the binding sites.
authors.affiliation: Bijvoet Center, Department of Bioorganic Chemistry, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: C Elizabeth P
authors.initials: CE
authors.lastname: Maljaars
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.forename: Koen M
authors.initials: KM
authors.lastname: Halkes
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.forename: Johannis P
authors.initials: JP
authors.lastname: Kamerling
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001212:Asialoglycoproteins / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D060748:Fetuins; D037483:Galectin 1 / Q000737:chemistry / Q000378:metabolism*; D037502:Galectin 3 / Q000737:chemistry / Q000378:metabolism*; D006020:Glycopeptides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D019151:Peptide Library; D011485:Protein Binding; D020349:Surface Plasmon Resonance / Q000379:methods*; D000509:alpha-Fetoproteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D001212:Asialoglycoproteins; D060748:Fetuins; D037483:Galectin 1; D037502:Galectin 3; D006020:Glycopeptides; C445499:LGALS1 protein, human; D008024:Ligands; D019151:Peptide Library; D000509:alpha-Fetoproteins; C017029:asialofetuin