Mono- and bivalent ligands bearing mannose 6-phosphate (M6P) surrogates

Targeting the M6P/ insulin-like growth factor II receptor

David B Berkowitz, Gourhari Maiti, Bradley D. Charette, Christine D. Dreis, Richard G MacDonald

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

(Chemical Equation Presented) Mannose 6-phosphate mimics locked into the α-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.

Original languageEnglish (US)
Pages (from-to)4921-4924
Number of pages4
JournalOrganic Letters
Volume6
Issue number26
DOIs
StatePublished - Dec 23 2004

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Bearings (structural)
IGF Type 2 Receptor
insulin
phosphates
Ligands
ligands
Phosphates
Organophosphonates
affinity
Alkenes
Hydrolases
Mannose
Oligosaccharides
Ether
Glycoproteins
metathesis
mannose-6-phosphate
alkenes
ethers
sectors

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Mono- and bivalent ligands bearing mannose 6-phosphate (M6P) surrogates : Targeting the M6P/ insulin-like growth factor II receptor. / Berkowitz, David B; Maiti, Gourhari; Charette, Bradley D.; Dreis, Christine D.; MacDonald, Richard G.

In: Organic Letters, Vol. 6, No. 26, 23.12.2004, p. 4921-4924.

Research output: Contribution to journalArticle

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