title: Synthesis and evaluation of xylopyranoside derivatives as "decoy acceptors" of human β-1,4-galactosyltransferase 7.
abstract: Proteoglycans (PGs), including heparan sulfate forms, are important regulators of tumor progression. In the PGs biosynthetic process, the core protein is synthesized on a ribosomal template and the sugar chains are assembled post-translationally, one sugar at a time, starting with the linkage of xylose to a serine residue of the core protein and followed by galactosidation of the xylosylprotein. Hydrophobic xylopyranosides have been previously shown to prime heparan sulfate synthesis, a property that was required to cause growth inhibition of tumor cells. To know if the antiproliferative activity of synthetic xylopyranosides is related to their ability to act as "decoy acceptors" of xylosylprotein 4-β-galactosyltransferase, we have heterologously expressed the catalytic domain of the human β-1,4-GalT 7 and studied the ability of a variety of synthetic xylopyranoside derivatives to act as substrates or inhibitors of the recombinant enzyme.
authors.affiliation: Departamento de Química Bioorgánica, Instituto de Química Orgánica General, CSIC, Madrid 28006, Spain.
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: García-García
authors.forename: Guillermo
authors.initials: G
authors.lastname: Corrales
authors.forename: Josefina
authors.initials: J
authors.lastname: Casas
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fernández-Mayoralas
authors.forename: Eduardo
authors.initials: E
authors.lastname: García-Junceda
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005700:Galactosyltransferases / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D006020:Glycopeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D006027:Glycosides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009237:N-Acetyllactosamine Synthase / Q000235:genetics / Q000378:metabolism*; D009284:Naphthols / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D012995:Solubility
chemical_list: C111149:2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside; D006020:Glycopeptides; D006027:Glycosides; D009284:Naphthols; D011994:Recombinant Proteins; C018069:galactosyltransferase acceptor; D005700:Galactosyltransferases; D009237:N-Acetyllactosamine Synthase