Mono-, di- and tri-antennary D-galactose ligands as competitive inhibitors and photoaffinity labels of the hexose transporting system in erythrocytes. A model for the irreversible blocking of receptors in cell membranes.
Starting from pentaerythritol, photolabile mono-, di-, and tri-dentate galactose derivatives as well as their 3H-labelled isotopomers were synthesised. The hydrophilic chains linking the 6 position of D-galactose to pentaerythritol consist of 13 atoms in line. The mono-, di- and tri-dentate compounds, although themselves not transported, inhibit in increasing order 14C-D-galactose transport into erythrocytes. On irradiating whole cells in the presence of ligand with 350-nm UV light, these compounds also in increasing order, could irreversibly block the hexose transport system. Irradiation without ligand has no effect. By using the 3H-labelled tridentate galactose compound the hexose transporter (zone 4.5) is specifically radiolabelled, as could be shown in an SDS-PAGE of membrane proteins from erythrocytes previously photoaffinity labelled. Radiolabelling is significantly suppressed in the presence of D-glucose.
Institut für Organische Chemie und Biochemie der Universität Freiburg, Germany.
J
J
Lehmann
M
M
Scheuring
D000345:Affinity Labels / Q000138:chemical synthesis* / Q000378:metabolism; D001667:Binding, Competitive; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D005690:Galactose / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000097:blood*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000345:Affinity Labels; D009004:Monosaccharide Transport Proteins; D011956:Receptors, Cell Surface; D005690:Galactose