Jump to main content
Jump to site search

Issue 12, 2014
Previous Article Next Article

Synthesis, broad spectrum antibacterial activity, and X-ray co-crystal structure of the decoding bacterial ribosomal A-site with 4′-deoxy-4′-fluoro neomycin analogs

Author affiliations

Abstract

This study reports the synthesis, antibacterial evaluation and nature of fluorine–rRNA contacts revealed by an X-ray co-crystal structure of a series of 4′-deoxy-4′-fluoro B-neomycin analogs. 4′-Deoxyfluorination improves the inhibition profile towards resistant enzymes and renders equally potent antibiotics compared to the parent neomycin B. The 4′-deoxy-4′-fluoro-4′-epi neomycin analogs showed a preferential inhibition over the 4′-deoxy-4′-fluoro neomycin counterpart against the strains of P. aeruginosa carrying a chromosomal APH(3′)-IIb enzyme, known to inactivate the parent aminoglycoside. To the best of our knowledge, this is the first example of a neighboring-group aminoglycoside-modifying enzyme evasion by fluorine substitution. A unique F-G1491 stacking was observed in a co-crystal structure of 4′-deoxy-4′-fluoro-4′-epi neomycin with a bacterial ribosomal RNA A-site.

Graphical abstract: Synthesis, broad spectrum antibacterial activity, and X-ray co-crystal structure of the decoding bacterial ribosomal A-site with 4′-deoxy-4′-fluoro neomycin analogs

Back to tab navigation
Please wait while Download options loads

Supplementary files

Publication details

The article was received on 02 Jun 2014, accepted on 16 Jul 2014 and first published on 27 Aug 2014


Article type: Edge Article
DOI: 10.1039/C4SC01626B
Citation: Chem. Sci., 2014,5, 4621-4632
  •   Request permissions

    Synthesis, broad spectrum antibacterial activity, and X-ray co-crystal structure of the decoding bacterial ribosomal A-site with 4′-deoxy-4′-fluoro neomycin analogs

    S. Hanessian, O. M. Saavedra, M. A. Vilchis-Reyes, J. P. Maianti, H. Kanazawa, P. Dozzo, R. D. Matias, A. Serio and J. Kondo, Chem. Sci., 2014, 5, 4621
    DOI: 10.1039/C4SC01626B

Search articles by author