Journal : Bioorg. Med. Chem. Lett.
Title : Inhibition of bacterial IF2 binding to fMet-tRNA((fMet)) by aminoglycosides.
Year : 2003
Volume : 13
Issue : 6
First Page : 993
Last Page : 996
Authors : Evans JM, Turner BA, Bowen S, Ho AM, Sarver RW, Benson E, Parker CN.
Abstract : 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.
