title: New synthetic cluster ligands for galactose/N-acetylgalactosamine-specific lectin of mammalian liver.
abstract: Synthetic ligands containing up to six residues of nonreducing terminal galactose were prepared. The synthesis involved coupling of carboxyl groups of N-benzyloxy-carbonylaspartic acid or of N-benzyloxycarbonyltyrosyl-gamma-glutamylglutamic acid to the omega-amino group of the aglycon of a glycoside that contained up to three lactosyl residues. The benzyloxycarbonyl group was removed by hydrogenolysis before these ligands were tested as inhibitors to the binding of 125I-asialoorosomucoid to the galactose/N-acetylgalactosamine lectin, both soluble and on the surface of freshly isolated mammalian hepatocytes. Each addition of a galactosyl residue to an existing ligand structure invariably increased the binding affinity of such a ligand. However, at each level of galactose valency, the binding constant varied as much as 1000-fold depending on the structure of the ligand. At a given level of valency, the binding strength of a cluster ligand depended mainly on two factors: (1) the maximum spatial inter-galactose distances and (2) the flexibility of the arm connecting galactosyl residues and the branch points. It has been postulated that the three galactose-combining sites of the lectin are arranged in space at the vertexes of a triangle whose sides are 15, 22, and 25 A [Lee, Y. C., Townsend, R. R., Hardy, M. R., Lönngren, J., & Bock, K. (1984) in Biochemical and Biophysical Studies of Proteins and Nucleic Acids (Lo, T. B., Liu, T. Y., & Li, C. H., Eds.) pp 349-360, Elsevier, New York]. Ligands having inter-galactose distances shorter than these lengths were invariably poor ligands at their respective level of valency.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000116:Acetylgalactosamine / Q000378:metabolism*; D000818:Animals; D001212:Asialoglycoproteins; D005688:Galactosamine / Q000031:analogs & derivatives*; D005690:Galactose / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000378:metabolism; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001212:Asialoglycoproteins; D008024:Ligands; D009844:Oligosaccharides; D009961:Orosomucoid; D011971:Receptors, Immunologic; C017030:asialoorosomucoid; C037045:galactose-N-acetylgalactosamine receptor; D005688:Galactosamine; D000116:Acetylgalactosamine; D005690:Galactose