August 2010
First Metal Complex of Active Site of Actinomycin-D
Metallomics, Issue 8


Isolation of the first metal complex of the active chromophore of the naturally occurring antibiotic Actinomycin D by CSCB researchers was one of the 10 most accessed papers in the RSC journal Metallomics in August 2010 and was featured on the front cover of the issue.

Naturally occurring Actinomycin-D inhibits DNA-directed RNA synthesis and is the first antibiotic shown to have anti-cancer activity.  The final step of the biosynthesis of Actinomycin D involves the oxidative coupling of o-aminophenol to form 2-aminophenoxazin-3-one and is catalysed by Phenoxazinone synthase, a laccase member of the blue copper oxidases.  Researchers have long been interested in the interaction of metal ions with the 2-aminophenoxazin-3-one chromophore which is the active component of the molecule.  PhD student Komala Pandurangan, working with Dr Grace Morgan, prepared 2-aminophenoxazin-3-one by a new route, before pursuing its coordination chemistry with a range of metal ions. As silver(I) complexes are potent antimicrobial agents in their own right,  and the ion is coordinatively and electronically non-demanding, silver was selected as the metal of choice.  The group were able to crystallize the silver complex and the structure was solved by CSCB crystallographer Dr Helge Müller-Bunz, shedding light on the preferred mode of coordination of the phenoxazinone.  The  antimicrobial activity of the silver complex was then investigated by Dr Francesca Paradisi who found it to be more active than that of the metal-free chromophore.

Image: Front Cover Metallomics August 2010

The work was funded by IRCSET (PhD studentship to Komala Pandurangan) and the synthetic and analytical facilities at the Centre for Synthesis and Chemical Biology (CSCB) at UCD, which enabled the team to perform the scientific work, were funded by the Higher Education Authority under PRTLI Cycle 3.

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