An α-mannose-6-phosphate (Man6P) ligand equipped with a terminal carboxylic acid through a high-molecular-weight PEG3000 spacer. The carboxylic acid can be activated to NHS, sulfo-NHS, or pentafluorophenyl esters and reacted with amine-functionalized platforms or lysine residues on proteins and peptides to form amide bonds. This compound enables the construction of lysosome-targeted therapeutics and research tools that exploit the mannose-6-phosphate receptor (M6PR), including applications in enzyme replacement therapy (ERT) for lysosomal storage disorders and in lysosome-targeting chimera (LYTAC) approaches for targeted protein degradation. The natural phosphate group provides authentic M6PR recognition, closely mimicking the endogenous Man6P glycan tag that directs newly synthesized lysosomal hydrolases to the lysosome.

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