Abstract: The present disclosure provides a class of compounds including a ligand moiety that specifically binds to a cell surface receptor, such as a folate receptor. The cell surface folate binding compound can trigger the receptor to internalize into the cell a bound compound. The ligand moieties of this disclosure can be linked to a variety of moieties of interest without impacting the specific binding to, and function of, the cell surface receptor, e.g., folate receptor. Also provided are compounds that are conjugates of the ligand moieties linked to a biomolecule, such as an antibody, which conjugates can harness cellular pathways to remove specific proteins of interest from the cell surface or from the extracellular milieu. Also provided herein are methods of using the conjugates to target a polypeptide of interest for sequestration and/or lysosomal degradation.

Abstract: The present disclosure provides a class of compounds including a ligand moiety that specifically binds to a cell surface asialoglycoprotein receptor (ASGPR). The cell surface ASGPR binding compounds can trigger the receptor to internalize into the cell a bound compound. The ligand moieties of this disclosure can be linked to a variety of moieties of interest without impacting the specific binding to, and function of, the cell surface receptor ASGPR. Also provided are compounds that are conjugates of the ligand moieties linked to a biomolecule, such as an antibody, which conjugates can harness cellular pathways to remove specific proteins of interest from the cell surface or from the extracellular milieu. Also provided herein methods of using the conjugates to target a polypeptide of interest for sequestration and/or lysosomal degradation.

Abstract: The present disclosure provides a class of compounds including a ligand moiety that specifically binds to a cell surface receptor, such as a mannose-6-phosphate receptor (M6PR) or a cell surface asialoglycoprotein receptor (ASGPR). The cell surface M6PR or ASGPR binding compounds can trigger the receptor to internalize into the cell abound compound. The ligand moieties of this disclosure can be linked to a variety of moieties of interest without impacting the specific binding to, and function of, the cell surface receptor, e.g., M6PR or ASGPR. Also provided are compounds that are conjugates of the ligand moieties linked to a biomolecule, such as an antibody, which conjugates can harness cellular pathways to remove specific proteins of interest from the cell surface or from the extracellular milieu. Also provided are methods of using the conjugates to target a polypeptide of interest for sequestration and/or lysosomal degradation.