Mono- and bivalent ligands bearing mannose 6-phosphate (M6P) surrogates: targeting the M6P/insulin-like growth factor II receptor.
[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.
Berkowitz
David B
DB
Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588-0304, USA. dbb@unlserve.unl.edu
Maiti
Gourhari
G
Charette
Bradley D
BD
Dreis
Christine D
CD
MacDonald
Richard G
RG
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*
D006023:Glycoproteins; D008024:Ligands; D008360:Mannosephosphates; D009844:Oligosaccharides; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate