MV100030
Tris-β-GalNAc-β-Ala-PEG3-N3
A triantennary N-acetylgalactosamine (Tri-GalNAcβ) ligand presenting three β-GalNAc residues on a tris-based branched scaffold, connected through a β-alanine linker and a hydrophilic triethylene glycol (PEG3) spacer to a terminal azide handle. The azide can be covalently coupled to alkyne partners via copper-catalyzed azide-alkyne cycloaddition (CuAAC), or to dibenzocyclooctyne (DBCO) and related strained alkynes using copper-free click chemistry, forming stable 1,2,3-triazole linkages.
This compound enables the construction of hepatocyte-targeted therapeutics and research tools that exploit the asialoglycoprotein receptor (ASGPR), which is highly expressed on liver hepatocytes and binds GalNAc-containing ligands with high affinity. The trivalent presentation of GalNAcβ residues engages multiple carbohydrate-recognition domains of ASGPR simultaneously, producing high-avidity binding that substantially exceeds the affinity of monovalent GalNAc ligands and closely mimics the geometry of clinically validated Tri-GalNAc targeting moieties used in approved GalNAc-siRNA therapeutics.