Monovalent and polyvalent carbohydrate inhibitors of ricin binding to a model of the cell-surface receptor.
A selection of galactose and lactose analogues was evaluated for their potency in inhibiting the binding of ricin to immobilised asialofetuin, which is a model of the cell-surface receptor for ricin. The aim was to identify compounds that could be used as antagonists of ricin toxicity in vivo, and as more selective, and therefore safer, antitoxins. Although one of these analogues had been identified by molecular modelling in a previous study as a potentially potent inhibitor, it and the other carbohydrates studied were less effective than galactose and lactose themselves (I(50) = 1.39 and 0.74 mM, respectively). In an attempt to increase the potency of carbohydrate-based inhibitors, galactose was coupled to the surface of dendrimers. No synergistic interactions were observed from this multivalent approach. Encouraging results, however, were obtained with a self-assembled lyotropic mesophase gel containing novel synthetic galactose-based surfactants, which was able to sequester ricin from aqueous solution in a 2-phase system.
Platforms Sciences Laboratory, Defence Science and Technology Organisation, Melbourne VIC 3001, Australia. ray.dawson@dsto.defence.gov.au
R M
RM
Dawson
M R
MR
Alderton
D
D
Wells
P G
PG
Hartley
D001212:Asialoglycoproteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D060748:Fetuins; D005690:Galactose / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007785:Lactose / Q000737:chemistry / Q000494:pharmacology*; D008954:Models, Biological; D015394:Molecular Structure; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012276:Ricin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D013329:Structure-Activity Relationship; D000509:alpha-Fetoproteins / Q000378:metabolism
D001212:Asialoglycoproteins; D050091:Dendrimers; D060748:Fetuins; D011956:Receptors, Cell Surface; D000509:alpha-Fetoproteins; C017029:asialofetuin; D012276:Ricin; D007785:Lactose; D005690:Galactose