Necessity of the sulfoxide moiety for the biochemical and biological properties of an analog of sparsomycin

An analog of the peptidyl transferase inhibitor sparsomycin was a competitive inhibitor (K i = 1.8 μM) of peptidyl-puromycin synthesis on E. , coli polysomes. Preincubation of polysomes with the compound enhanced the degree of inhibition of peptide bond formation. A model for the involvement of a histidine residue in peptidyl transferase activity is presented as a result of our observations which include direct association of [ 3H] labelled analog with 70S ribosomes. The correct oxidation state of sulfur in the compound was necessary for the “preincubation effect” and entry of the compound into bacterial cells.