title: 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.
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, United States.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Jared
authors.initials: J
authors.lastname: Marshall
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Nicola
authors.initials: N
authors.lastname: Edwards
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000378:metabolism; D002240:Carbohydrate Sequence; D008024:Ligands; D008360:Mannosephosphates / Q000138:chemical synthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D021381:Protein Transport; D017527:Receptor, IGF Type 2 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate; D000117:Acetylglucosamine