Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Peptidyl transferase inhibition

Aminohexose Nucleosides. The 4-aminohexose nucleosides (128—140) are Hsted in Table 7 (1—4,240—242). A biosynthetic relationship between the 4-aminohexose peptidyl nucleoside antibiotics and the pentopyranines has been proposed (1). The 4-aminohexose pyrimidine nucleoside antibiotics block peptidyl transferase activity and inhibit transfer of amino acids from aminoacyl-tRNA to polypeptides. Hikizimycin, gougerotin, amicetin, and blasticidin S bind to the peptidyl transferase center at overlapping sites (243). [Pg.129]

Bacterial ribosome function Aminoglycosides Tetracyclines Chloramphenicol Macrolides, azalides Fusidic acid Mupirocin Distort SOS ribosomal subunit Block SOS ribosomal subunit Inhibits peptidyl transferase Block translocation Inhibits elongation factor Inhibits isoleucyl-tRNA synthesis No action on 40S subunit Excluded by mammalian cells No action on mammalian equivalent No action on mammalian equivalent Excluded by mammalian cells No action on mammalian equivalent... [Pg.163]

These agents bind selectively to a region of the SOS ribosomal subunit close to that of chloramphenicol and erythromycin. They block elongation of the peptide chain by inhibition of peptidyl transferase. [Pg.172]

The answer is b. (Hardman, p 1131.) Chloramphenicol inhibits protein synthesis in bacteria and, to a lesser extent, in eukaryotic cells. The drug binds reversibly to the. 505 ribosomal subunit and prevents attachment of aminoacybtransfer RNA (tRNA) to its binding site. The amino acid substrate is unavailable for peptidyl transferase and peptide bond formation. [Pg.81]

Puromycin inhibits both prokaryotic and eukaryotic translation by binding to the A site. Peptidyl transferase attaches the peptide to puromycin, and the peptide with puromycin attached at the C-terminus is released, prematurely terminating chain growth. [Pg.54]

Chloramphenicol is able to inhibit the peptidyl transferase reaction and so bacterial protein synthesis by binding reversibly to the 50s ribosomal subunit. Resistance can occur due to the plasmid-mediated enzyme chloramphenicol acetyltransferase which inactivates the drug by acetylation. Such resistance is often a part of plasmid-mediated multidrug resistance. Resistance can also occur by an altered bacterial permeability. However in most instances resistance to chloramphenicol only develops slowly and remains partial. [Pg.415]

Similar to macrolides, lincosamides also target the SOS ribosome subunit. More specifically, they inhibit the enzyme peptidyl transferase, which in turn inhibits the activity of ribosomes, preventing the binding of amino acyl-tRNA to the A site on the SOS subunit. That activity blocks the synthesis of proteins. [Pg.37]

Inhibits peptide bond formation by binding to the SOS ribosomal subunit, inhibiting peptidyl transferase. [Pg.3]

Narciclasine (215) is an antitumor agent which exerts an antimitotic effect during metaphase by immediately terminating protein synthesis in eukaryotic cells at the step of peptide bond formation (97,101,141,142), apparently by interaction with the ansiomycin area of the ribosomal peptidyl transferase center (142). The alkaloid has also been found to inhibit HeLa cell growth and to stabilize HeLa cell polysomes in vivo (97). Although DNA synthesis was retarded by narciclasine, RNA synthesis was practically unaffected (97,142). Sev-... [Pg.296]

To stop the translation reaction and further stabilize the ribosomal complexes, cycloheximide can be added in the eukaryotic system (Gersuk et al., 1997). For the same purpose chloramphenicol, an antibiotic that inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA in the peptidyl transferase center, can be used in the E. coli system (Mattheakis et al., 1994). However, chloramphenicol was found to have no influence on the efficiency of E. coli ribosome display (Hanes and Pluckthun, 1997). [Pg.383]

The drug binds to the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction. Because of the similarity of mammalian mitochondrial ribosomes to those of bacteria, protein synthesis in these organelles may be inhibited at high circulating chloramphenicol levels, producing bone marrow toxicity. [Pg.331]

Cethromycin (ABT-773) 39 (Advanced Life Sciences) had an NDA filed in October 2008 for the treatment of CAP.67 Advanced Life Sciences is also evaluating cethromycin 39 against other respiratory tract infections and in pre-clinical studies as a prophylactic treatment of anthrax post-exposure. Cethromycin 3968 70 is a semi-synthetic ketolide derivative of erythromycin 4071 originally synthesised by Abbott Laboratories,72 which like erythromycin 40, inhibits bacterial protein synthesis through binding to the peptidyl-transferase site of the bacterial 50S ribosomal subunit. Important macrolide antibiotics in clinical use today include erythromycin 40 itself, clarithromycin, azithromycin and, most recently, telithromycin (launched in 2001). [Pg.330]

Most antibiotics that inhibit the function of the SOS subunit bind near its peptidyl transferase center (Fig. 4.4) and block peptide bond formation. Crystal structures are available for several such antibiotics bound to the ribosome (Fig. 4.5). They appear to inhibit the peptidyl transferase reaction either by competing directly with its substrates for binding, or indirectly by blocking the exit tunnel. [Pg.104]

The bound macrolides almost completely occlude the peptide exit tunnel, which explains the two distinctive characteristics of macrolide inhibition. Firstly, the reason that macrolides do not inhibit ribosomes that are already actively making protein is that the nascent peptide in the exit tunnel blocks access to the macrolide binding site. Secondly, the reason macrolides do not directly inhibit the peptidyl transferase reaction is that they bind near to, but not directly at, the active site. Only after a few peptide bonds are formed will the peptide contact the bound macrolide and be blocked from further elongation. As a result, short di-, tri- and tetra-peptides will accumulate. [Pg.107]

The prototypical aminoacylated nucleoside analogue antibiotic is puromycin which inhibits the protein translation in all three domains of life. The chemical structure of puromycin is the same as that of tyrosylated adenosine, except for the presence of three added methyl groups and the replacement of an ester bond with an amide bond (Fig. 4.11). Puromycin mimics tyrosyl-tRNA so well that it binds to the A-site and gets incorporated into an elongating peptide. This leads to termination of translation because puromycin terminated peptides fall off the ribosome. Puromycin derivatives have been used crystallographically as peptidyl transferase substrates and have contributed to our understanding of the structure of the peptidyl transferase site (Fig. 4.5) [11, 16, 45],... [Pg.117]

Kirillov, S., Porse, B.T, Vester, B., Woolley, P., Garrett, R.A., Movement of the 3 -end of tRNA through the peptidyl transferase centre and its inhibition by antibiotics. FEES Lett. 1997, 406, 223-233. [Pg.124]

Porse, B., Rodriguez-Fonseca, C., Le-viEv, I., Garrett, R.A., Antibiotic inhibition of the movement of tRNA substrates through a peptidyl transferase cavity. Biochem. Cell Biol. 1995, 73, 877-885. [Pg.124]

Chloramphenicol Inhibits the peptidyl transferase activity of the 50S ribosomal subunit (prokaryotes)... [Pg.1237]


See other pages where Peptidyl transferase inhibition is mentioned: [Pg.515]    [Pg.1088]    [Pg.372]    [Pg.172]    [Pg.172]    [Pg.288]    [Pg.12]    [Pg.182]    [Pg.45]    [Pg.576]    [Pg.313]    [Pg.1012]    [Pg.1067]    [Pg.1069]    [Pg.123]    [Pg.755]    [Pg.130]    [Pg.203]    [Pg.1055]    [Pg.266]    [Pg.279]    [Pg.172]    [Pg.138]    [Pg.1088]    [Pg.190]    [Pg.356]    [Pg.55]    [Pg.1235]    [Pg.230]    [Pg.73]   
See also in sourсe #XX -- [ Pg.151 ]




SEARCH



Peptidyl

Peptidyl transferase

© 2024 chempedia.info