Targeting Metalloproteins by Fragment-Based Lead Discovery (pages 211–223)
Sherida Johnson, Elisa Barile, Biancamaria Farina, Angela Purves, Jun Wei, Li-Hsing Chen, Sergey Shiryaev, Ziming Zhang, Irina Rodionova, Arpita Agrawal, Seth M. Cohen, Andrei Osterman, Alex Strongin and Maurizio Pellecchia
Article first published online: 16 JUN 2011 | DOI: 10.1111/j.1747-0285.2011.01136.x
We describe a novel fragment based drug discovery approach using a metal targeting fragment library. The library is based on a variety of distinct classes of metal-binding groups designed to reliably anchor the fragments at the target’s metal ions. We demonstrate that the approach can effectively identify novel, potent and selective agents that can be readily natured into lead molecules for metalloprotein-targeted therapeutics.