Logo of aacPermissionsJournals.ASM.orgJournalAAC ArticleJournal InfoAuthorsReviewers
Antimicrob Agents Chemother. Oct 1997; 41(10): 2127–2131.
PMCID: PMC164081

The oxazolidinone eperezolid binds to the 50S ribosomal subunit and competes with binding of chloramphenicol and lincomycin.


The oxazolidinones are a novel class of antibiotics that act by inhibiting protein synthesis. It as been reported that the drug exerts its primary activity on the initiation phase of translation. In order to study the possibility of direct interaction between the drug and the ribosome, we have developed a binding assay using 14C-labelled eperezolid (PNU-100592; formerly U-100592). Eperezolid binds specifically to the 50S ribosomal subunit of Escherichia coli. The specific binding of eperezolid is dose dependent and is proportional to the ribosome concentrations. Scatchard analysis of the binding data reveals that the dissociation constant (Kd) is about 20 microM. The binding of eperezolid to the ribosome is competitively inhibited by chloramphenicol and lincomycin. However, unlike chloramphenicol and lincomycin, eperezolid does not inhibit the puromycin reaction, indicating that the oxazolidinones have no effect on peptidyl transferase. In addition, whereas lincomycin and, to some extent, chloramphenicol inhibit translation termination, eperezolid has no effect. Therefore, we conclude that the oxazolidinones inhibit protein synthesis by binding to the 50S ribosomal subunit at a site close to the site(s) to which chloramphenicol and lincomycin bind but that the oxazolidinones are mechanistically distinct from these two antibiotics.

Full Text

The Full Text of this article is available as a PDF (245K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Barbachyn MR, Hutchinson DK, Brickner SJ, Cynamon MH, Kilburn JO, Klemens SP, Glickman SE, Grega KC, Hendges SK, Toops DS, et al. Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity. J Med Chem. 1996 Feb 2;39(3):680–685. [PubMed]
  • Barry AL. In vitro evaluation of DuP 105 and DuP 721, two new oxazolidinone antimicrobial agents. Antimicrob Agents Chemother. 1988 Jan;32(1):150–152. [PMC free article] [PubMed]
  • Brickner SJ, Hutchinson DK, Barbachyn MR, Manninen PR, Ulanowicz DA, Garmon SA, Grega KC, Hendges SK, Toops DS, Ford CW, et al. Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant gram-positive bacterial infections. J Med Chem. 1996 Feb 2;39(3):673–679. [PubMed]
  • Brumfitt W, Hamilton-Miller JM. Antibacterial oxazolidinones. In vitro activity of a new analogue, E3709. Diagn Microbiol Infect Dis. 1992 Sep-Oct;15(7):621–625. [PubMed]
  • Cannon M. The puromycin reaction and its inhibition by chloramphenicol. Eur J Biochem. 1968 Dec;7(1):137–145. [PubMed]
  • Cundliffe E, McQuillen K. Bacterial protein synthesis: the effects of antibiotics. J Mol Biol. 1967 Nov 28;30(1):137–146. [PubMed]
  • Daly JS, Eliopoulos GM, Reiszner E, Moellering RC., Jr Activity and mechanism of action of DuP 105 and DuP 721, new oxazolidinone compounds. J Antimicrob Chemother. 1988 Jun;21(6):721–730. [PubMed]
  • Daly JS, Eliopoulos GM, Willey S, Moellering RC., Jr Mechanism of action and in vitro and in vivo activities of S-6123, a new oxazolidinone compound. Antimicrob Agents Chemother. 1988 Sep;32(9):1341–1346. [PMC free article] [PubMed]
  • Douthwaite S. Interaction of the antibiotics clindamycin and lincomycin with Escherichia coli 23S ribosomal RNA. Nucleic Acids Res. 1992 Sep 25;20(18):4717–4720. [PMC free article] [PubMed]
  • Eustice DC, Feldman PA, Zajac I, Slee AM. Mechanism of action of DuP 721: inhibition of an early event during initiation of protein synthesis. Antimicrob Agents Chemother. 1988 Aug;32(8):1218–1222. [PMC free article] [PubMed]
  • Eustice DC, Feldman PA, Slee AM. The mechanism of action of DuP 721, a new antibacterial agent: effects on macromolecular synthesis. Biochem Biophys Res Commun. 1988 Feb 15;150(3):965–971. [PubMed]
  • Fernandez-Munoz R, Monro RE, Torres-Pinedo R, Vazquez D. Substrate- and antibiotic-binding sites at the peptidyl-transferase centre of Escherichia coli ribosomes. Studies on the chloramphenicol. lincomycin and erythromycin sites. Eur J Biochem. 1971 Nov 11;23(1):185–193. [PubMed]
  • Ganoza MC, Buckingham K, Hader P, Neilson T. Effect of base sequence on in vitro protein-chain termination. J Biol Chem. 1984 Nov 25;259(22):14101–14104. [PubMed]
  • Mini E, Novelli A, Mazzei T, Periti P. Comparative in vitro activity of the new oxazolidinones DuP 721 and DuP 105 against staphylococci and streptococci. Eur J Clin Microbiol Infect Dis. 1989 Mar;8(3):256–260. [PubMed]
  • Moazed D, Noller HF. Chloramphenicol, erythromycin, carbomycin and vernamycin B protect overlapping sites in the peptidyl transferase region of 23S ribosomal RNA. Biochimie. 1987 Aug;69(8):879–884. [PubMed]
  • NATHANS D, LIPMANN F. Amino acid transfer from aminoacyl-ribonucleic acids to protein on ribosomes of Escherichia coli. Proc Natl Acad Sci U S A. 1961 Apr 15;47:497–504. [PMC free article] [PubMed]
  • Pongs O, Bald R, Erdmann VA. Identification of chloramphenicol-binding protein in Escherichia coli ribosomes by affinity labeling. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2229–2233. [PMC free article] [PubMed]
  • Randall-Hazelbauer LL, Kuland CG. Identification of three 30S proteins contributing to the ribosomal A site. Mol Gen Genet. 1972;115(3):234–242. [PubMed]
  • Slee AM, Wuonola MA, McRipley RJ, Zajac I, Zawada MJ, Bartholomew PT, Gregory WA, Forbes M. Oxazolidinones, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721. Antimicrob Agents Chemother. 1987 Nov;31(11):1791–1797. [PMC free article] [PubMed]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...