Calpains: Attractive targets for the development of synthetic inhibitors
| dc.contributor.author | Pietsch, M. | |
| dc.contributor.author | Chua, K. | |
| dc.contributor.author | Abell, A. | |
| dc.date.issued | 2010 | |
| dc.description.abstract | The physiological roles of calpains are discussed, as are the associated pathological disorders that result from their over-activation. We also present practical information for establishing functional inhibition assays and an overview of X-ray crystal structures of calpain-inhibitor complexes to aid inhibitor design. These structures reveal the expected extended β-strand conformation for the inhibitor backbone, a geometry that has been engineered into inhibitors with the introduction of either an N-terminal heterocycle or a macrocycle that links the P<sub>1</sub> and P<sub>3</sub> residues. The structure and function of all the main classes of inhibitors are reviewed, with most examples being classified according to the nature of the C-terminal reactive warhead group that reacts with the active site cysteine of calpains. These inhibitor classes include epoxysuccinate derivatives, aldehydes, aldehyde prodrugs (hemiacetals) and α-keto carbonyl compounds. Inhibitors derived from the endogenous inhibitor calpastatin and examples lacking a warhead, are now known and these are also discussed. | |
| dc.description.statementofresponsibility | Markus Pietsch, Krystle C.H. Chua, Andrew D. Abell | |
| dc.identifier.citation | Current Topics in Medicinal Chemistry, 2010; 10(3):270-293 | |
| dc.identifier.doi | 10.2174/156802610790725489 | |
| dc.identifier.issn | 1568-0266 | |
| dc.identifier.issn | 1873-4294 | |
| dc.identifier.orcid | Abell, A. [0000-0002-0604-2629] | |
| dc.identifier.uri | http://hdl.handle.net/2440/59374 | |
| dc.language.iso | en | |
| dc.publisher | Bentham Science Publ Ltd | |
| dc.relation.grant | http://purl.org/au-research/grants/arc/DP0771901 | |
| dc.relation.grant | http://purl.org/au-research/grants/arc/DP0771901 | |
| dc.rights | Copyright Bentham Science Publishers Ltd. | |
| dc.source.uri | https://doi.org/10.2174/156802610790725489 | |
| dc.subject | β-strand conformation | |
| dc.subject | Calpain | |
| dc.subject | calpain assay | |
| dc.subject | calpastatin | |
| dc.subject | crystal structure | |
| dc.subject | cysteine protease | |
| dc.subject | macrocycles | |
| dc.subject | protease inhibitors | |
| dc.title | Calpains: Attractive targets for the development of synthetic inhibitors | |
| dc.type | Journal article | |
| pubs.publication-status | Published |