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Structure-based combinatorial library design: discovery of non-peptidic inhibitors of caspases 3 and 8 |
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| Authors: | Head M S Ryan M D Lee D Feng Y Janson C A Concha N O Keller P M deWolf W E |
| Institution: | (1) Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, USA;(2) Discovery Chemistry US, SmithKline Beecham Pharmaceuticals, USA;(3) Structural Biology, SmithKline Beecham Pharmaceuticals, USA;(4) Mechanistic Enzymology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA, 19406 |
| Abstract: | Structure-based design of a combinatorial array was carried out in order to identify non-peptidic thiomethylketone inhibitors of caspases 3 and 8. Five compounds from the designed array were active against caspase 3, and two were active against caspase 8. A 2.5-Å  resolution co-crystal structure of caspase 3 and a thiomethylketone array member is reported. The structure-based design strategy has proved useful for identifying caspase inhibitors. |
| Keywords: | caspase 3 caspace 8 inhibitors structure-based design combinatorial library |
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