DL-threo-beta-fluoroasparagine inhibits asparagine-linked glycosylation in cell-free lysates.
The effect of beta-fluoroasparagine on N-linked glycosylation was examined in a cell-free translation system in which glycosylation is coupled to protein synthesis. The threo-isomer markedly inhibited glycosylation at a concentration of 1 mM, and this effect was blocked by L-asparagine, indicating that glycosylation was inhibited secondary to incorporation of the asparagine analog into protein. The erythro-isomer, at similar concentrations, was not incorporated into protein and had no effect on glycosylation. threo-beta-Fluoroasparagine is highly toxic to some mammalian cells in culture. Our observations suggest that its toxicity may be due in part to the failure of the fluoroasparagine-containing protein to become glycosylated. The data suggest that this analog will be useful for examining the structural determinants for glycosylation.
D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002287:Carcinoma, Krebs 2 / Q000378:metabolism; D002474:Cell-Free System; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006027:Glycosides / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics
D006023:Glycoproteins; D006027:Glycosides; D012313:RNA; D001216:Asparagine; C023464:beta-fluoroasparagine