Inhibition of bacterial IF2 binding to fMet-tRNA (fMet) by aminoglycosides

Screening for inhibitors of bacterial protein synthesis Initiation Factor 2 (IF2) binding to N-formyl-Methionyl-transfer RNA (fMet-tRNA (fMet)) identified a series of aminoglycosides, that included amikacin and kanamycin A1, as inhibitors of this interaction. Subsequent testing revealed that aminoglycosides displayed a wide range of inhibitory activity. However, the failure of these compounds to completely inhibit binding of IF2 to fMet-tRNA (fMet), the known ability of aminoglycosides to bind RNA, and the ability of the aminoglycosides to displace PicoGreen bound to fMet-tRNA (fMet) suggest these compounds act by binding fMet-tRNA (fMet). This hypothesis is further supported by isothermal denaturation experiments that failed to show any interaction between the IF2 protein and the aminoglycosides. The inhibition of bacterial Initation Factor 2 binding to N-formyl-methionine transfer RNA by aminoglycosides such as amikacin, IC 50 1μM, is reported.