title: Mono- and bivalent ligands bearing mannose 6-phosphate (M6P) surrogates: targeting the M6P/insulin-like growth factor II receptor.
abstract: [reaction: see text] Mannose 6-phosphate mimics locked into the alpha-configuration and bearing hydrolase-resistant phosphate surrogates were synthesized and evaluated for binding affinity to the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R). Affinity increases as the phosphate surrogate is varied in the order malonyl ether < malonate < phosphonate. An alkene cross-metathesis approach to sought-after bivalent M6P-bearing ligands is also described. These compounds were designed to map onto biantennary sectors of high-mannose-type oligosaccharides carried by glycoprotein M6P/IGF2R ligands.
authors.affiliation: Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588-0304, USA. dbb@unlserve.unl.edu
authors.forename: David B
authors.initials: DB
authors.lastname: Berkowitz
authors.forename: Gourhari
authors.initials: G
authors.lastname: Maiti
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Charette
authors.forename: Christine D
authors.initials: CD
authors.lastname: Dreis
authors.forename: Richard G
authors.initials: RG
authors.lastname: MacDonald
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006023:Glycoproteins / Q000737:chemistry; D008024:Ligands; D008360:Mannosephosphates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry; D017527:Receptor, IGF Type 2 / Q000187:drug effects*
chemical_list: D006023:Glycoproteins; D008024:Ligands; D008360:Mannosephosphates; D009844:Oligosaccharides; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate