Inhibition of nucleoside-binding sites by nucleoside analogues in Escherichia coli

Abstract

Nucleoside analogues modified in heterocyclic bases or sugar moieties were screened for their ability of counter-acting the bacteriostatic effect of showdomycin in E. coli. Pyrimidine ribonucleosides or 2′-deoxyribonucleosides sub-stituted at the position 5 with halogen, atom, methyl or hydroxyl group, 2′-fluoro-, 2′-chloro-2′-deoxyuridine and its 5-methyl homologue, N⁴-dimethylcytidine and N⁴-acetylcytidine, isocytidine, 1-(β-D-ribofuranosyl)-4-aminopyrimidine-6-one, isoguanosine, purine riboside, the N⁶- and 8-substituted derivatives of adenosine, were all effective. With the exception of 5-hydroxyuridine, all these compounds were non-toxic in E. coli. The same group of compounds was shown to inhibit competitively the phosphorolysis of 2′-deoxythymidine in whole cells, being inactive in cell-free extracts. The analogues apparently compete for a common nucleoside-binding site at the surface of the cells. Showdomycin itself does not cause any irreversible inactivation of nucleoside-binding sites.