FACILE SYNTHESIS OF A HIGH-AFFINITY LIGAND FOR MAMMALIAN HEPATIC LECTIN CONTAINING 3 TERMINAL N-ACETYLGALACTOSAMINE RESIDUES

A simple cluster glycoside containing three residues of N-acetylgalact osamine with proper inter-residual distances can be a high-affinity li gand for asialoglycoprotein receptor of mammalian liver. YEE(ah-GalNAc )(3) [Lee, R. T., and Lee, Y. C. (1987) Glycoconjugate J. 4, 317-328] is such a ligand having a K-d in the subnanomolar range, and this high -affinity ligand has been successfully utilized in the delivery of gen e to the parenchymal cells of the liver [Merwin, J. R., Noell, G. S., Thomas, W. L., Chiou, H. C., DeRome, M. E., McKee, T. D., Spitalny, G. L., and Findeis, M. A. (1994) Bioconjugate Chem. 5, 612-620; Hangelan d, J. J., Levis, J. T., Lee, Y. C., and Ts'o, P. O. P. (1995) Bioconju gate Chem. 6, 695-701]. Reported here is a synthetic procedure for an equally effective, homologous trivalent ligand, YDD(G-ah-GalNAc)(3). T he advantage offered by this new cluster glycoside is that the synthet ic scheme accomplishes purification of reaction intermediates and the product without chromatographic separations. This greatly simplifies t he procedure and allows scale-up of the operation at reduced cost of p roduction.