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SUMMARY:Catalytic MetalloDrugs – New Therapies for Old Problems - Profes
 sor James Cowan\, Ohio State University
DTSTART:20120330T130000Z
DTEND:20120330T140000Z
UID:TALK37277@talks.cam.ac.uk
CONTACT:Jonathan Goddard
DESCRIPTION:Catalytic metallodrugs combine a reactive metal center with a 
 recognition motif for a structured nucleic acid or protein therapeutic tar
 get\, and demonstrate effective and selective cleavage or modification che
 mistry. Reactivity is highly dependent on factors that include metal reduc
 tion potential\, coordination unsaturation\, overall charge\, the ability 
 of the metal complexes to facilitate generation of ROS\, and the degree to
  which these ROS are either metal-coordinated or diffusible. In contrast t
 o nucleic acid targets that undergo backbone scission\, enzyme inactivatio
 n appears to arise through oxidative damage to amino acid sidechains in th
 e active site.  Reactivity stems primarily from metal associated reactive 
 oxygen species.\nCatalytic metallodrugs embody several unique advantages o
 ver traditional drug “inhibitors” – namely\, the target is eliminate
 d\, multiturnover activity allows a sub-stoichiometric concentration of ca
 talyst relative to target\, improved selectivity\, and reduced potential f
 or resistance. Application of this strategy to HCV\, HIV\, bacterial and c
 ardiovascular protein and RNA targets will be discussed\, including soluti
 on and cellular assays\, and studies of animal models.  
LOCATION:Pfizer Lecture Theatre\, Department of Chemistry
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