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

摘要

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-alpha-GalNAcAc(3))Glu and Fmoc-Tyr-OH to obtain YEE(ah-GalNAc)(3) with a total yield of 83%. [References: 27]