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Bioorg Med Chem. 2007 Feb 1;15(3):1330-40. Epub 2006 Nov 10.

Parallel solid synthesis of inhibitors of the essential cell division FtsZ enzyme as a new potential class of antibacterials.

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CREFSIP, Département de Biologie Médicale, Faculté de médecine, Université Laval, Sainte-Foy, Que., Canada G1K 7P4.


As a model system for designing new inhibitors of bacterial cell division, we studied the essential and highly conserved FtsZ GTPase from Pseudomonas aeruginosa. A collection of GTP analogues were prepared using the solid-phase parallel synthesis approach. The synthesized GTP analogues inhibited the GTPase activity of FtsZ with IC(50) values between 450microM and 2.6mM, and 5 compounds inhibited Staphylococcus aureus growth in a biological assay. The FtsZ spectrophotometric assay developed for screening of synthesized compounds is the first step in identification of antibacterials targeting the bacterial cell division essential proteins.

[Indexed for MEDLINE]

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