TY - JOUR
T1 - Synthesis of novel bivalent mimetic ligands for mannose-6-phosphate receptors
AU - Liu, Yunpeng
AU - Marshall, Jared
AU - Li, Qiong
AU - Edwards, Nicola
AU - Chen, Gong
N1 - Funding Information:
This work is supported by The Pennsylvania State University, Glycomimetics Inc, and The Center for LignoCellulose Structure and Formation, an Energy Frontier Research Center funded by the US Department of Energy, Office of Science under Award Number DE-SC0001090.
PY - 2013/4/15
Y1 - 2013/4/15
N2 - 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.
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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U2 - 10.1016/j.bmcl.2013.02.068
DO - 10.1016/j.bmcl.2013.02.068
M3 - Article
C2 - 23473680
AN - SCOPUS:84875427019
SN - 0960-894X
VL - 23
SP - 2328
EP - 2331
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 8
ER -