Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/59374
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Type: Journal article
Title: Calpains: Attractive targets for the development of synthetic inhibitors
Author: Pietsch, M.
Chua, K.
Abell, A.
Citation: Current Topics in Medicinal Chemistry, 2010; 10(3):270-293
Publisher: Bentham Science Publ Ltd
Issue Date: 2010
ISSN: 1568-0266
1873-4294
Statement of
Responsibility: 
Markus Pietsch, Krystle C.H. Chua, Andrew D. Abell
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.
Keywords: β-strand conformation
Calpain
calpain assay
calpastatin
crystal structure
cysteine protease
macrocycles
protease inhibitors
Rights: Copyright Bentham Science Publishers Ltd.
DOI: 10.2174/156802610790725489
Grant ID: http://purl.org/au-research/grants/arc/DP0771901
http://purl.org/au-research/grants/arc/DP0771901
Published version: http://dx.doi.org/10.2174/156802610790725489
Appears in Collections:Aurora harvest
Chemistry publications

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