Inhibition of [14C]chloramphenicol binding to Escherichia coli ribosomes by erythromycin derivatives.

The effect of erythromycin A and 35 analogues of erythromycin A on [(14)C]chloramphenicol binding to Escherichia coli ribosomes was evaluated. Substitutions on various portions of the erythromycin molecule were made with retention of ability to bind to ribosomes. Specifically, substantial activity in interference with [(14)C]chloramphenicol binding was retained upon removal of the cladinose and various substitutions on the 3-hydroxyl, the oxime, and 2-hydroxyl groups. Erythromycin analogues with relatively poor binding activity to ribosomes could be detected. This assay can be used alone or in conjunction with microbiological assays for screening of active analogues. It permits an estimate of the general binding activity of compounds rapidly and directly. The assay reflects the ability of the compounds to interact with their target organelle, the ribosome, and may serve as a useful adjunct in developing new compounds.