Protein bacterial synthesis inhibitors

Aminoglycoside a structurally complex antibacterial that works as bacterial protein synthesis inhibitor. 

Tetracycline one of a class of antibacterials based on a tetracyclic skeleton and that act as a bacterial protein synthesis inhibitors. 

A number of antibiotics in addition to the folate antagonists and sulfonamides are modestly active antimalarials. The antibiotics that are bacterial protein synthesis inhibitors appear to act against malaria parasites by inhibiting protein synthesis in a plasmodial prokaryote-like organelle, the apicoplast. None of the antibiotics should be used as single agents in the treatment of malaria because their action is much slower than that of standard antimalarials. 

Brandi, L., Lazzaroni, A., Cavalletti, L., Abbondi, M., Corti, E., Ciciliato, I., Gastaldo, L., Marazzi, A., Feroggio, M., Maio, A., Colombo, L., Donadio, S., Marinelli, F., Losi, D., Gualerzi, C. O., and Selva, E. (2006c). Novel tetrapeptide inhibitors of bacterial protein synthesis produced by a streptomyces. Biochemistry 43, 3700—3710. 

Newer and more generally usefnl macrolide antibiotics include azithromycin (Zithromax) and clarithromycin (Biaxin). These too are wide-spectrum antibiotics and both are semisynthetic derivatives of erythromycin. Like the tetracyclines, the macrolide antibiotics act as protein synthesis inhibitors and also do so by binding specifically to the bacterial ribosome, thongh at a site distinct from that of the tetracyclines. 

Alice et al studied the turnover kinetics of Listeria OTonocytogenex-secreted p60 protein (a murein hydrolase) by host cell cytosolic proteasomes. J774 cells, seeded in flasks and incubated overnight in culture medium, were infected with log-phase cultures of E. monocytogenes for 30 min, washed, and incubated in culture medium for 3 h, with gentamicin (50 tg/ml) added after the first 30 min to inhibit extracellular bacterial growth. Cells then were washed and placed in methionine-free medium with spectinomycin, gentamicin, the eukaryotic protein synthesis inhibitors [cycloheximide (50 tg/mL) and anisomycin (30 tg/ml),] and 25 dVI calpain inhibitor I. After 30 min, [ S]methionine was added, and the cells were pulse-labeled for periods of 20 to 60 min. Cells... 

Mupirocin is not related to any of the sys-temically used antibiotics. It is an inhibitor of bacterial protein synthesis and is especially active against gram-positive aerobic bacteria, e.g. methicillin-resistant S. aureus and group A beta-hemolytic streptococci. Absorption through the skin is minimal. Intranasal application may be associated with irritation of mucous membranes. 

Erythromycin Prevents bacterial protein synthesis by binding to the 50S ribosomal subunit Bacteriostatic activity against susceptible bacteria Community-acquired pneumonia t pertussis corynebacterial, and chlamydial infections Oral, IV hepatic clearance (half-life 1.5 h) dosed every 6 h cytochrome P450 inhibitor Toxicity Gastrointestinal upset, hepatotoxicity, QTC prolongation... 

Inhibitors are substances that tend to decrease the rate of an enzyme-catalysed reaction. Although some act on the substrate, the discussion here will be restricted to those inhibitors which combine directly with the enzyme. Inhibitors have many uses, not only in the determination of the characteristics of enzymes, but also in aiding research into metabolic pathways where an inhibited enzyme will allow metabolites to build up so that they are present in detectable levels. Another important use is in the control of infection where drugs such as sulphanilamides competitively inhibit the synthesis of tetrahydrofolates which are vitamins essential to the growth of some bacteria. Many antibiotics are inhibitors of bacterial protein synthesis (e.g. tetracyclin) and cell-wall synthesis (e.g. penicillin). 

Berninamycinic acid is one of the products from acid hydrolysis of the cyclic peptide antibiotic berninamycin A, which is a potent inhibitor of bacterial protein synthesis. Berninamycinic acid has been assigned the structure (524), anhydro-3,8-dicarboxy-6-hydroxythiazolo[2,3-/][l,6]naphthyridin-4-ium hydroxide. The 6-hydroxy group arises during hydrolysis from a peptide-bonded amino group (77JA1645). 

Mukhtar TA, Wright GD. Streptogramins, oxazolidinones, and other inhibitors of bacterial protein synthesis. Chem. Rev. 2005 105 529-542. 

Bacterial infections are treated with antibiotics. There are many antibiotics available, but they fall into three major groups based on their mode of action inhibitors of bacterial nucleic acid synthesis inhibitors of cell wall synthesis and inhibition of bacterial protein synthesis. Resistance of bacteria to commonly-used antibiotics has become a major problem necessitating the development of new antibiotics. Tuberculosis infection is difficult to treat and requires a combination of at least three different antibiotics. 

Table 26.1. Bacterial and Eukaryotic Protein Synthesis Inhibitors...

The protein synthesis inhibitors tetracycline, chloramphenicol, and streptomycin all block bacterial protein synthesis. Several eukaryotic translational inhibitors have also been found and they include diphtheria toxin, ricin, and cycloheximide. Puromycin causes premature chain termination in both prokaryotes and eukaryotes by functioning as an aminoacyl tRNA analog. 

Greenwood, D. (1995). Inhibitors of bacterial protein synthesis. In Antimicrobial Chemotherapy, 3rd ed. (D. Greenwood, Ed.), pp. 32-48. Oxford University Press, Oxford. 

Tetracyclines (Table 46-1) are inhibitors of bacterial protein synthesis. 

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