Antibiotics protein synthesis inhibitors

Lactam Antibiotics Ribosomal Protein Synthesis Inhibitors... 

Ribosomal Protein Synthesis Inhibitors. Figure 5 Nucleotides at the binding sites of chloramphenicol, erythromycin and clindamycin at the peptidyl transferase center. The nucleotides that are within 4.4 A of the antibiotics chloramphenicol, erythromycin and clindamycin in 50S-antibiotic complexes are indicated with the letters C, E, and L, respectively, on the secondary structure of the peptidyl transferase loop region of 23S rRNA (the sequence shown is that of E. coll). The sites of drug resistance in one or more peptidyl transferase antibiotics due to base changes (solid circles) and lack of modification (solid square) are indicated. Nucleotides that display altered chemical reactivity in the presence of one or more peptidyl transferase antibiotics are boxed. 

Inhibitors of protein synthesis 4 The problem of antibiotic resistance... 

Urease assay. When Proteus mirabilis grows in a urea-containing medium it hydrolyses the urea to ammonia and consequently raises the pH of the medium. This production of urease is inhibited by aminoglycoside antibiotics (inhibitors of protein synthesis Chapter 8). In practice, it is difficult to obtain reliable results by this method. 

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. 

Nucleocidin (LXXX) [353], an adenine nucleoside antibiotic whose structure has recently been elucidated, is also a potent inhibitor of protein synthesis. Studies with this compouna have led to the conclusion that nucleocidin forms a complex with ribosomes which is inactive in peptide bond formation. Binding... 

Proliferation Inhibitor of DNA polymerase-gamma (e.g., nucleoside reverse transcriptase inhibitors) inhibition of mitochondrial protein synthesis (e.g., oxazolidinone antibiotics) mitochondrial DNA mutation (e.g.. oxidative injury by ethanol)... 

Infections by the ulcer-causing bacterium Helicobacter pylori can be treated effectively with a prolonged course of doxycycline or another of the tetracycline family of antibiotics, potent inhibitors of prokaryotic protein synthesis. 

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. 

The selection of transformed chloroplasts usually involves the use of an antibiotic resistance marker. Spectinomycin is used most routinely because of the high specificity it displays as a prokaryotic translational inhibitor as well as the relatively low side effects it exerts on plants. The bacterial aminoglycoside 3 -adenyltransferase gene (ciadA) confers resistance to both streptomycin and spectinomycin. The aadA protein catalyzes the covalent transfer of an adenosine monophosphate (AMP) residue from adenosine triphosphate (ATP) to spectinomycin, thereby converting the antibiotic into an inactive form that no longer inhibits protein synthesis for prokaryotic 70S ribosomes that are present in the chloroplast. 

It is a peptide protein synthesis inhibitor antibiotic isolated from Streptomyces capreolus. It is second line antimycobacterial drug which exhibits activity against human strains of Mycobacterium tuberculosis. 

Capreomycin is a peptide protein synthesis inhibitor antibiotic obtained from Streptomyces capreolus. Daily injection of 1 g intramuscularly results in blood levels of 10 mcg/mL or more. Such concentrations in vitro are inhibitory for many mycobacteria, including multidrug-resistant strains of M tuberculosis. 

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. 

Antibiotics as Inhibitors of Nucleic Acid and Protein Synthesis G. Hartmann et al., Angew. Chem., Int. Ed. Engl., 1968, 7, 693-701. 

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). 

The structures of some antibiotic inhibitors of protein synthesis. All of the inhibitors shown function by binding to specific sites on the ribosome. 

Clough B, Rangachari K, Strath M, Preiser PR, Wilson RJM (1999) Antibiotic Inhibitors of Organellar Protein Synthesis of Plasmodium falciparum. Protist 150 189... 

Monti F, Ripamonti F, Hawser SP, Islam K (1999) Aspirochlorine A Highly Selective and Potent Inhibitor of Fungal Protein Synthesis. J Antibiot 52 311... 

Little work has been done on the effect of anabolic inhibitors on cellular heat dissipation probably because there is empirical evidence that anabolic processes do not contribute significantly to it (see p. 312). Loike et al. (1981) found that 0.07 mmol dm-3 cycloheximide, an antibiotic inhibitor of protein synthesis, had no effect in 30 minutes on the heat production of murine macrophages. On the other hand, Krakauer and Krakauer (1976) showed that long-term exposure of lymphocytes from immunized horses to 1 mg dm-3 cycloheximide considerably reduced heat production. This was likely to be due to a secondary effect of the antibiotic arresting catabolism by inhibiting the turnover of short half-life enzymes. 

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). 

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