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Mono- and bivalent ligands bearing mannose 6-phosphate (M6P) surrogates: targeting the M6P/insulin-like growth factor
David B Berkowitz1, Gourhari Maiti, Bradley D Charette
1Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588-0304, USA. dbb@unlserve.unl.edu
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.
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