Peptide, synthesis inhibition

Obrig, T. G., Culp, W. J., McKeehan, W. L., and Hardesty, B. (1971). The mechanism by which cycloheximide and related glutarimide antibiotics inhibit peptide synthesis on reticulocyte ribosomes. J. Biol. Chem. 246, 174-181. 

Friulimicins - antimicrobial peptides that inhibit peptidoglycan synthesis... 

Note that the protein kinase, which phosphorylates the IF-GDP complex is structurally similar to the protein kinase that is activated by double-stranded RNA, i.e. the genome of some viruses. This protein kinase phosphorylates the IF-GDP complex in an infected host cell, so that viral peptide synthesis is inhibited and the virus cannot multiply. Synthesis of this kinase is stimulated by the cytokine, interferon, which is released by virus-infected cells as an early-warning system to adjacent cells not yet infected (Chapter 17 see Figure 17.32). 

Pharmacology Ethionamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. The exact mechanism of action of ethionamide has not been fully elucidated, but the drug appears to inhibit peptide synthesis in susceptible organisms. 

Mechanism of Action An antitubercular agent that inhibits peptide synthesis. Therapeutic Effect Suppresses mycobacterial multiplication. Bactericidal. Pharmacokinetics Rapidly absorbed from the gastrointestinal (Gl) tract. Widely distributed. Protein binding 10%. Metabolized in liver. Primarily excreted in urine. Removed by hemodialysis. Half-life 2-3 hr (half-life is increased with impaired renal function). 

A. General description Eptifibatide is a cyclic heptapeptide containing six amino acids and one mercaptopropionyl residue. An interchain disulfide bridge is formed between the cysteine amide and the mercaptopropionyl moieties. Eptifibatide binds to the platelet receptor glycoprotein (gp) Ilb/IIIa of human platelets and inhibits platelet aggregation. The eptifibatide peptide is produced by solution-phase peptide synthesis, and is purified by preparative reverse-phase liquid chromatography and lyophifized. 

Zubay, G., M. Lederman, and J. DeVries, DNA-directed peptide synthesis III. Repression of jS-galactosidase synthesis and inhibition of repressor by inducer in a cell-free system. Proc. Natl. Acad. Sci. USA 58 1669-1675, 1967. Showing that repressor works in a cell-free system. 

Similar to the effect on restraint stress, RmHA (10 mg/kg x 2 ip) inhibited the ACTH and P-END response to insulin-induced hypoglycemia, which increases neuronal HA turnover [30-31]. This inhibitory effect was completely or partly reversed by THIOP. Likewise, the responses of the POMC-derived peptides and corticosterone to immune stimulation with the E.coli lipopolysaccharide (LPS) endotoxin, which augmented neuronal HA turnover, were reduced by RmHA pretreatment [39]. The effect of RmHA was equal to that of HA synthesis inhibition by a-FMH [39]. In lactating female rats suckling-induced ACTH secretion was reduced by pretreatment with RmHA (Fig. 6) as well as by a-FMH [32],... 

The patent application as drafted contains a description of how to make the specifically disclosed peptides as well as additional description explaining that it was well within the purview of one of ordinary skill in the art to make hexapep-tide amino acid sequences by standard synthesis, solid phase peptide synthesis or synthesis by recombinant techniques. The patent application also described the in vitro BACE inhibition assay and the data generated from it. The application further explains ... 

The solution-phase synthesis and resolution of new phosphinopeptidic building blocks containing a triple bond and their involvement in 1,3-dipolar cycloaddition with a variety of in j// -prepared nitrile oxides allowed the diastereoselective preparation of a novel class of isoxazole-containing phosphinic peptides 619. Inhibition assays of some of these peptides revealed their behavior as very potent inhibitors of metalloproteases, outmatching previously reported phosphinic peptides in terms of potency <2003CEJ2079>. 

This model of the active site of transpeptidase has been used for the "rational" design of a novel antibacterial agent. A transition-state analog of the natural substrates inhibits bacterial peptide synthesis iji vitro.66... 

In mammalian cells, an elevation In the cytosolic cAMP level stimulates the expression of many genes. For instance, increased cAMP in certain endocrine cells Induces production of somatostatin, a peptide that inhibits release of various hormones in liver cells, cAMP Induces synthesis of several enzymes involved in converting three-carbon compounds to glucose. 

Protein synthesis inhibition results from reversible binding of the tetracycline drugs to the 30S ribosomal subunit. This in turn prevents the attachment of aminoacyl-fRNAs to the acceptor site of the ribosomal structure (Fig. 6-17). The ribosomal mRNA complex is thus effectively precluded from initiating protein synthesis. Tetracyclines do not interfere with actual peptide bond formation, nor with the translocation process. In vitro studies with 70S ribosomes using photoaffinity techniques demonstrate binding to the 4S and 18S protein components of the 30S subunits. It is likely that these are the actual binding sites. 

Ethionamide is an antituberculosis agent that causes inhibition of peptide synthesis in susceptible organisms. It is indicated in the treatment of tuberculosis, in combination with other agents, in patients with M. tuberculosis resistant to isoniazid or rifampin, or when there is intolerance to other antituberculous agents. 

Nowadays, antibiotics are primarily classified according to the mechanism of their action, with similarity of chemical structure as a secondary factor. Penicillin and its derivatives inhibit the formation of bacterial cell walls (Fig. 3.38). Cephalosporins have the same active mechanism. Other compounds are taken up into bacterial DNA to form unstable molecules (quinolones, metronidazole) or inhibit peptide synthesis (tetracychnes, aminoglycosides, macrolides). Some antibiotics (e.g. glycopeptides) exert a complex effect. 

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