Synthesis and evaluation of xylopyranoside derivatives as “decoy acceptors” of human β-1,4-galactosyltransferase 7

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.E. G-J. and A. F-M. thank the Spanish Ministerio de Ciencia e Innovacio´ n (Grants CTQ2007-67403/BQU and CTQ2010- 15418) and Comunidad de Madrid (Grant S2009/PPQ-1752) for financial support. J. C. has been supported by the Spanish Ministerio de Ciencia e Innovacio´ n (Grant SAF2008-00706) and Generalitat de Catalunya (Grant 2009SGR-1072). J.F. G-G. was supported by a predoctoral I3P fellowship of the European Social Fund. We thank Mrs Eva Dalmau for excellent technical assistance.Peer reviewe