Exploiting differences in caspase-2 and-3 S 2 subsites for selectivity: Structure-based design, solid-phase synthesis and in vitro activity of novel substrate-based …

…, F Krieger, M Meniconi, I Muñoz-Sanjuán…

Index: Maillard, Michel C.; Brookfield, Frederick A.; Courtney, Stephen M.; Eustache, Florence M.; Gemkow, Mark J.; Handel, Rebecca K.; Johnson, Laura C.; Johnson, Peter D.; Kerry, Mark A.; Krieger, Florian; Meniconi, Mirco; Munoz-Sanjuan, Ignacio; Palfrey, Jordan J.; Park, Hyunsun; Schaertl, Sabine; Taylor, Malcolm G.; Weddell, Derek; Dominguez, Celia Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 19 p. 5833 - 5851

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Citation Number: 15

Abstract

Several caspases have been implicated in the pathogenesis of Huntington's disease (HD); however, existing caspase inhibitors lack the selectivity required to investigate the specific involvement of individual caspases in the neuronal cell death associated with HD. In order to explore the potential role played by caspase-2, the potent but non-selective canonical Ac- VDVAD-CHO caspase-2 inhibitor 1 was rationally modified at the P2 residue in an attempt ...