https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2874%2980689-7

Inhibitors of protein synthesis

https://mmbr.asm.org/content/mmbr/33/2/264.full.pdf

Mechanism of protein biosynthesis.

In rel+ strains of Escherichia coli guanosine 2′(3′)-diphosphate-5′-diphosphate (ppGpp) was found to accumulate (a) during amino acid starvation of an auxotrophic strain, (b) during heating to the non-permissive temperature of a valSts strain, (c) during heating of a wild-type strain to temperatures above 46°C and (d) during treatment with trimethoprim or hydroxylamine. A rapid decay of the accumulated ppGpp was observed after addition of chloramphenicol, tetracycline, fusidic acid, erythromycin, puromycin or colicin E3 to susceptible cultures. All of these antibiotics give a rapid and complete inhibition of protein synthesis. Streptomycin showed a delayed inhibitory action on protein synthesis and had little effect on the level of accumulated ppGpp. The addition of rifampicin also results in a delayed decay of ppGpp.



These results indicate that the synthesis of ppGpp is independent of RNA synthesis, but suggest that a coupling exists between ppGpp formation and an idling reaction of one of the initiation steps of protein synthesis.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1972.tb01916.x

Metabolism of guanosine tetraphosphate in Escherichia coli

Amino acid antagonists with proven or potentially inhibitory activities on aminoacyl-tRNA synthetases were tested for their antiproliferative effect against Escherichia coli B. The compds. 4- and 6-fluorotryptophan, 5-methyltryptophan, selenocysteine, and beta -(2-thienyl)alanine gave strong growth inhibition in minimal medium, which disappeared after the addn. of structurally related natural amino acids or in an enriched broth. The inhibitory effect on aminoacyl-tRNA synthetases and the minimal inhibitory concn. for growth inhibition in minimal medium could not be correlated.

Investigations on the antiproliferative effects of amino acid antagonists targeting for aminoacyl-tRNA synthetases. Part II--The antileukemic effect.

Most of the known antibiotics act at the level of protein biosynthesis probably due to the extraordinary complexity of the translational machinery which can be interfered with at many points. At first a survey is given of our present knowledge covering the structure and function of the prokaryotic ribosome. The most important antibiotics acting at the translational level are integrated into this network of data. The binding sites and the inhibition mechanisms of the drugs, together with the ribosomal components altered in resistant mutants are described. Finally, the points of interference with the translational machinery are indicated in an extended scheme of ribosomal functions.

Klein A

Papers

Inhibition of peptide-chain initiation in Escherichia coli by hydroxylamine and effects on ribonucleic acid synthesis.