ACTION OF THIAZOLIDINE-2-CARBOXYLIC ACID, A PROLINE ANALOG, ON PROTEIN SYNTHESIZING SYSTEMS

Thiazolidine-2-carboxylic acid, or β-thiaproline, is a proline analog in which the β methylene group of proline is substituted by a sulfur atom. It has been demonstrated that β-thiaproline is activated and transferred to tRNAPro by Escherichia coli and rat liver aminoacyl-tRNA synthetases, and inhibits proline incorporation into polypeptides in protein synthesizing systems from E. coli, rat liver or rabbit reticulocytes. In mammalian systems β-thiaproline inhibits also leucine incorporation; in rabbit reticulocyte lysate it inhibits ribosome run-off. Both these effects may be explained by the fact that β-thiaproline once incorporated into the growing polypeptide chain impairs its further elongation, as shown by experiments made with puromycin. All tests were performed in comparison with thiazolidine-4-carboxylic acid, or γ-thiaproline, another proline analog having the γ methylene group substituted by a sulfur atom; it was shown that in all the reactions studied both compounds act as competitive inhibitors of proline. Some differences in the effects of the two analogs have been evidenced: in almost all the reactions and mainly in the whole protein synthesizing systems, β-thiaproline shows an higher inhibitory activity. © 1979.