title: Synthesis and application of alpha-D-mannosyl clusters as photoaffinity ligands for mannose-binding proteins: concanavalin A as a model receptor.
abstract: Mono-, di-, and tri-antennary alpha-D-mannopyranosyl derivatives were synthesized as oligosaccharide mimics. The compounds vary in the length of the acyclic aglyconic spacers linking, in the case of the di- and tri-antennary derivatives, the glycosyl endgroups. By haemagglutination assay (Coombs test) the affinity of the alpha-D-mannopyranosyl ligands against Con A was determined in comparison with methyl alpha-D-mannopyranoside. Affinity enhancement and strong cross-linking capacity were found with the di- and tri-antennary compounds where alpha-D-mannopyranosyl endgroups are separated by spacers of 5-37 atoms in length. The optimal ligand had Ki of 5.1 microM in comparison with 3.12 microM for methyl alpha-D-mannopyranoside. The monoantennary compound and, to certain extents, one di- and short tri-antennary ligands with short spacer lengths did not differ significantly in affinity from methyl alpha-D-mannopyranoside. A triantennary, radiolabelled ligand equipped with a photolabile diazirino group was used to covalently modify Con A by photoaffinity labelling. A significant degree of covalent cross-linking of Con A monomers was observed.
authors.affiliation: Institut für Organische Chemie und Biochemie, Universität Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Lehmann
authors.forename: U P
authors.initials: UP
authors.lastname: Weitzel
mesh_terms: D000345:Affinity Labels / Q000138:chemical synthesis*; D001391:Azo Compounds / Q000138:chemical synthesis; D002352:Carrier Proteins / Q000378:metabolism*; D003208:Concanavalin A / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006386:Hemagglutination Tests; D009682:Magnetic Resonance Spectroscopy; D037241:Mannose-Binding Lectins; D008362:Mannosides / Q000138:chemical synthesis*; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis*; D011485:Protein Binding
chemical_list: D000345:Affinity Labels; D001391:Azo Compounds; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D037241:Mannose-Binding Lectins; D008362:Mannosides; D009844:Oligosaccharides; D003208:Concanavalin A