Facile solid phase synthesis of YEE(ah-GalNAc)₃, a ligand with known high affinity for the asialoglycoprotein receptor

A simple cluster glycoside, containing three residues of N- acetylgalactosamine with proper inter-residual distances, can be a high- affinity ligand for the asialoglycoprotein receptor (ASGPr) of mammalian liver. Tris(GalNAc-aminohexyl)glycoside of tyrosyl(glutamyl)glutamate YEE(ah- GalNAc)₃ 1, which is known to have sub-nanomolar affinity for the asialoglycoprotein receptor, was efficiently synthesized by using succinic acid as a linker to anchor GalNAc-aminohexyl glycoside to solid phase resin, followed by coupling the building blocks of Fmoc-(ah-α-GalNAcAc₃)Glu and Fmoc-Tyr-OH to obtain YEE(ah-GalNAc)₃ with a total yield of 83%.