MV100014
Tris-GalNAc-Ahx-NH2
A triantennary N-acetylgalactosamine (Tri-GalNAcβ) ligand presenting three β-GalNAc residues on a tris-based branched scaffold, extended through a 6-aminohexanoic acid (Ahx) spacer to a terminal primary amine. The Ahx spacer provides extended spatial separation between the Tri-GalNAc cluster and the conjugation site, and the primary amine couples with NHS-activated esters, carboxylic acids, and other amine-reactive groups to form stable amide bonds. This compound enables the construction of hepatocyte-targeted therapeutics and research tools that exploit the asialoglycoprotein receptor (ASGPR; Ashwell-Morell receptor), 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.