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Reductive heme-dependent activation of the n-oxide prodrug AQ4N by nitric oxide synthase.

ABSTRACT: Anaerobic reduction of anticancer prodrugs is a promising route to achieve targeting and selectivity in anticancer drug design. Most reductive prodrug activations involve simple electron transfer from a flavoprotein and are not amenable to specific targeting. Here, we report that the N-oxide AQ4N is reduced by a nitric oxide synthase. This reduction involves interaction with the heme iron atom in the active site and is thus subject to specific protein constraints.

SUBMITTER: Nishida CR

PROVIDER: S-EPMC2730118 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Reductive heme-dependent activation of the n-oxide prodrug AQ4N by nitric oxide synthase.

Nishida Clinton R CR Ortiz de Montellano Paul R PR

Journal of medicinal chemistry 20080806 16

Anaerobic reduction of anticancer prodrugs is a promising route to achieve targeting and selectivity in anticancer drug design. Most reductive prodrug activations involve simple electron transfer from a flavoprotein and are not amenable to specific targeting. Here, we report that the N-oxide AQ4N is reduced by a nitric oxide synthase. This reduction involves interaction with the heme iron atom in the active site and is thus subject to specific protein constraints. ...[more]

PMID: 18681417

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