Metal-mediated inhibition is a viable approach for inhibiting cellular methionine aminopeptidase.

Bioorg. Med. Chem. Lett.2009 Dec 15;19(24):6862-4. Epub 2009 Oct 23

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Methionine aminopeptidase (MetAP) plays an essential role for cell survival. Hence, MetAP is a promising target for developing broad spectrum antibacterial agents. MetAP can be activated in vitro by a number of divalent metals, and X-ray structures show that the active site can accommodate two cations. Herein, we demonstrate bacterial growth inhibition by a compound that targets MetAP by recruitment of a third auxiliary metal. Contrary to previous beliefs, this shows that metal-mediated inhibition is a viable approach for discovering MetAP inhibitors that are effective for therapeutic application.

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Metal-mediated inhibition is a viable approach for inhibiting cellular methionine aminopeptidase.

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