Tethering identifies fragment that yields potent inhibitors of human caspase-1.

Research paper by Bruce T BT Fahr, Tom T O'Brien, Phuongly P Pham, Nathan D ND Waal, Subramanian S Baskaran, Brian C BC Raimundo, Joni W JW Lam, Michelle M MM Sopko, Hans E HE Purkey, Michael J MJ Romanowski

Indexed on: 09 Nov '05Published on: 09 Nov '05Published in: Bioorganic & Medicinal Chemistry Letters


Disulfide Tethering was applied to the active site of human caspase-1, resulting in the discovery of a novel, tricyclic molecular fragment that selectively binds in S4. This fragment was developed into a class of potent inhibitors of human caspase-1. Several key analogues determined the optimal distance of the tricycle from the catalytic residues, the relative importance of various features of the tricycle, and the importance of the linker.