PMID: 7086840May 1, 1982Paper

DL-threo-beta-Fluoroaspartate and DL-threo-beta-fluoroasparagine: selective cytotoxic agents for mammalian cells in culture

Journal of Medicinal Chemistry
A M SternR H Abeles

Abstract

Absolute configuration assignments have been made for the diastereomers of DL-beta-fluoroaspartate by X-ray analysis. The cytotoxicity of these isomers against various mammalian cells was examined. DL-threo-beta-Fluoroaspartate shows selective cytotoxicity. Growth of the most sensitive cells is completely inhibited by 13 micrometers DL-threo-beta-fluoroaspartate in the presence of 100 micrometers L-aspartate, a component of the culture medium. A difference in the rate of transport of DL-beta-fluoroaspartate among the cells studied is an important factor determining cell specificity. For those cells that are sensitive to DL-beta-fluoroaspartate, the threo isomer is, in all cases, more potent than the erythro isomer. Radioactivity derived from L-threo-beta-fluoro[14C]aspartate is incorporated into proteins at a rate comparable to the rate of incorporation from L-[14C]aspartate. We synthesized DL-threo-beta-fluoroasparagine. This compound is also cytotoxic but less specific and less potent than DL-threo-beta-fluoroaspartate. However, the cell specificity can be enhanced in the presence of 1 mM L-aspartate, which can protect some cells but not others from the cytotoxic effects of DL-threo-beta-fluoroasparagine. Jensen sarcoma cells...Continue Reading

Citations

Apr 5, 1984·Biochimica Et Biophysica Acta·M J Wilson, D L Hatfield
Jun 24, 1987·Biochimica Et Biophysica Acta·H A KaplanW J Lennarz
Jun 23, 2010·PloS One·Gabriël J L Beckers, Manfred Gahr
Nov 20, 2015·PLoS Computational Biology·Jordi FonollosaMikhail Rabinovich
Apr 26, 2012·PLoS Computational Biology·Raoul-Martin Memmesheimer, Marc Timme
Mar 29, 2008·PLoS Computational Biology·Ilya NemenmanRob R de Ruyter van Steveninck

Related Concepts

Beta-fluoroaspartic acid, hydrochloride, (threo)-isomer
Beta-fluoroasparagine
Antineoplastic Agents
Asparagine
Aspartic Acid, Magnesium-Potassium (2:1:2) Salt
Neoplasms, Experimental
Molecular Stereochemistry
Structure-Activity Relationship
X-Ray Diffraction

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