Synthetic analogs of aurodox and kirromycin active on elongation factor Tu from Escherichia coli.

The activities of kirromycin oxime, aurodox 2,4-dinitrophenylhydrazone and four O-derivatives of aurodox have been compared to those of kirromycin (mocimycin) and its natural N-methyl analog aurodox in the in vitro system of E. coli. All synthetic derivatives were able to inhibit protein biosynthesis like the original antibiotics. Moreover, the analogs did promote all the effects of kirromycin on the reactions dependent on elongation factor Tu. From these results it can be concluded that the acidic hydroxyl and keto functions of kirromycin and aurodox are not directly involved in the action of the antibiotics on elongation factor Tu and can, thus, be chemically modified without loss of activity. In most cases, however, derivatization lowered the affinity of the antibiotic for elongation factor Tu. This suggests that the pyridone moiety of kirromycin and aurodox and the first part of its side chain should play a role in the association of these antibiotics with elongation factor Tu.