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

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.

journal_name

Bioorg Med Chem Lett

authors

Liu Y,Marshall J,Li Q,Edwards N,Chen G

doi

10.1016/j.bmcl.2013.02.068

subject

Has Abstract

pub_date

2013-04-15 00:00:00

pages

2328-31

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00244-8

journal_volume

23

pub_type

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