Synthesis of novel bivalent mimetic ligands for mannose-6-phosphate receptors

Yunpeng Liu, Jared Marshall, Qiong Li, Nicola Edwards, Gong Chen

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Mannose-6-phosphate (M6P)-containing N-linked glycans are essential signaling molecules for sorting hydrolases in eukaryotic cells. Their receptors, especially the cation-independent M6P receptors (CI-MPRs), have emerged as promising protein targets for targeted drug delivery for the treatment of lysosomal storage disease and liver fibrosis. In this Letter, we describe the design and synthesis of novel bivalent mimetic ligands for CI-MPRs. We report that for the first time, a newly-discovered binding motif, GlcNAc-M6P, has been incorporated in mimetic ligands. M6P- and GlcNAc-M6P-containing building blocks, equipped with NH2 and CO2H handles, have been prepared and assembled with an ornithine linker through amide coupling reactions. Efficient global deprotection protocols have also been developed which have been showcased in the synthesis of our novel bivalent mimetic ligands.

Original languageEnglish (US)
Pages (from-to)2328-2331
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number8
DOIs
StatePublished - Apr 15 2013

Fingerprint

IGF Type 2 Receptor
Ligands
Cations
Lysosomal Storage Diseases
Ornithine
Eukaryotic Cells
Hydrolases
Sorting
Amides
Liver Cirrhosis
Liver
Polysaccharides
Molecules
mannose-6-phosphate
Pharmaceutical Preparations
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Liu, Yunpeng ; Marshall, Jared ; Li, Qiong ; Edwards, Nicola ; Chen, Gong. / Synthesis of novel bivalent mimetic ligands for mannose-6-phosphate receptors. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 8. pp. 2328-2331.
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Synthesis of novel bivalent mimetic ligands for mannose-6-phosphate receptors. / Liu, Yunpeng; Marshall, Jared; Li, Qiong; Edwards, Nicola; Chen, Gong.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 8, 15.04.2013, p. 2328-2331.

Research output: Contribution to journalArticle

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AB - Mannose-6-phosphate (M6P)-containing N-linked glycans are essential signaling molecules for sorting hydrolases in eukaryotic cells. Their receptors, especially the cation-independent M6P receptors (CI-MPRs), have emerged as promising protein targets for targeted drug delivery for the treatment of lysosomal storage disease and liver fibrosis. In this Letter, we describe the design and synthesis of novel bivalent mimetic ligands for CI-MPRs. We report that for the first time, a newly-discovered binding motif, GlcNAc-M6P, has been incorporated in mimetic ligands. M6P- and GlcNAc-M6P-containing building blocks, equipped with NH2 and CO2H handles, have been prepared and assembled with an ornithine linker through amide coupling reactions. Efficient global deprotection protocols have also been developed which have been showcased in the synthesis of our novel bivalent mimetic ligands.

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