Inhibition of protein biosynthesis

Aminoglycosides Tetracyclines Chloramphenicol Erythromycin Clindamycin Spectinomycin Mupirodn Fusldfc add Inhibition of protein biosynthesis... 

The covalent trapping of the enzyme leads to a depletion of the cellular pool of DNMTs and subsequent DNA hypomethylation. This in turn results in activation with respect to the reactivation of silenced genes. Additionally, the covalently trapped DNMT may inhibit RNA and DNA polymerases, which leads to an inhibition of protein biosynthesis and DNA strand breaks. This may lead to apoptosis and hence cytotoxicity. Thus, it is not easy to dissect the reasons for the clinical efficacy of these inhibitors in terms of real epigenetic and plain cytotoxic effects [81]. 

In certain situations, e.g., inhibition of protein biosynthesis, TNF receptor activation has a proapoptotic effect, however, in that caspases are activated and cell death is initiated. 

There are two commercial fungicides, the antibiotics blasticidin S and kasugamycin, that act via the inhibition of protein biosynthesis (Figure 4.19). Blasticidin S is a fermentation product obtained from cultures of Streptomyces griseochromogenes, and has specific activity in the control of P. oryzae, similar to kasugamycin, a secondary metabolite of S. kasugaensis. However, much of the earlier work on mode of action was carried out using another antibiotic, cycloheximide. 

ANTIBIOTICS ELFAMYCINS. The elfamyans are so named because they exhibit antimicrobial activity through the inhibition of protein biosynthesis via binding to the Wongation factor Tu. All of the known elfamyans are listed in Table 1. These antibiotics are distinguished by low mammalian toxicity, narrow-range antimicrobial activity, and positive effects on feed utilization and growth promotion in farm animals. Elfamyans also improve milk production in lactatmg ruminants. 

The mode of action of the harringtonines has been investigated. All inhibit protein synthesis in eukaryotic cells (190-192). The principal effect of harringtonine was inhibition of protein biosynthesis in HeLa cells (193). Homoharringtonine, a potential antineoplastic alkaloid (191), was cytotoxic in HeLa, KB, and L cells growing in monolayer cell cultures (194). 

The literature is replete with reports of minor inhibitions of some biochemical or physiological process by chemotherapeutic drugs. In my own laboratory it was found that quinacrine caused a slight inhibition of protein biosynthesis in susceptible bacteria which subsequently was verified in a cell-free poly U system, polymerizing phenylalanine 18 Since it was also established, however, that the drug is a strong inhibitor of DNA biosynthesis 17 and that this effect accounts for the bactericidal action of quinacrine, the slight effect on protein biosynthesis was not mistaken as the mode of action. 

Inhibitions of protein synthesis were subsequently confirmed by chemical analyses for protein in growing bacterial cultures38, 39. Figure 439 shows the specific inhibition of protein biosynthesis by chloramphenicol in E. coli and the continuation of RNA ( ribose ) and DNA biosynthesis for an experimental period of 50 minutes. Similar results have been typically obtained with other inhibitors of protein biosynthesis. 

Fig. 4. Selective inhibition of protein biosynthesis in E. coli by 1.9 x 10 4 M chloramphenicol39 ...

Chloramphenicol is bacteriostatic by virtue of inhibition of protein biosynthesis in both bacterial and, to a lesser extent, host ribosomes. Chloramphenicol binds to the SOS subparticle in a region near where the macrolides and lincosamides bind (Fig. 38.24). 

H. has antimycotic activity against pathogenic yeasts through inhibition of protein biosynthesis. Its biosynthesis proceeds from acetyl-CoA and activated aspartic acid. ... 

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