TY - JOUR T1 - Inhibition by Chloramphenicol rowth o in <em>Escherichia coli</em> JF - Molecular Pharmacology JO - Mol Pharmacol SP - 158 LP - 170 VL - 2 IS - 2 AU - H. K. DAS AU - AVRAM GOLDSTEIN AU - LEE C. KANNER Y1 - 1966/04/01 UR - http://molpharm.aspetjournals.org/content/2/2/158.abstract N2 - Inhibition of protein synthesis by chloramphenicol has been studied in intact cells of Escherichia coli at 37° and at 0°. The drug has no effect upon the association of ribosomes and messenger RNA, and no preferential effect upon the initiation of new protein chains or upon chain termination and detachment from ribosomes. The primary action of the drug is to block the addition of new residues to the growing nascent protein chains, which remain attached to the ribosomes. There appears to be no selective blockade of the addition of any particular amino acid, nor is there preferential inhibition of the synthesis of any particular kind of protein. Chloramphenicol is bound to ribosomes at 0°in the same concentration range in which it produces a graded inhibition of protein synthesis. A possible mechanism is proposed, whereby chloramphenicol might act by competing with the carboxy-terminal amino acid of the growing chain of nascent protein (attached to transfer-RNA) for a stereospecific locus associated with one of the transfer-RNA binding sites on the ribosome. ACKNOWLEDGMENTS We are indebted to Mrs. Louise I. Lowney for expert assistance in various phases of this investigation, and to Joel B. Kirschbaum for carrying out incorporation experiments with several amino acids. These studies were supported by research grant CA02797 from the National Cancer Institute and training grant GM322 from the National Institute of General Medical Sciences, U.S. Public Health Service. ER -