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Type: Journal article
Title: Tripeptide analogues of MG132 as protease inhibitors
Author: Pehere, A.D.
Nguyen, S.
Garlick, S.K.
Wilson, D.W.
Hudson, I.
Sykes, M.J.
Morton, J.D.
Abell, A.D.
Citation: Bioorganic and Medicinal Chemistry, 2019; 27(2):436-441
Publisher: Elsevier
Issue Date: 2019
ISSN: 0968-0896
Statement of
Ashok D. Pehere, Steven Nguyen, Sarah K. Garlick, Danny W. Wilson, Irene Hudson, Matthew J. Sykes, James D. Morton, Andrew D. Abell
Abstract: The 26S proteasome and calpain are linked to a number of important human diseases. Here, we report a series of analogues of the prototypical tripeptide aldehyde inhibitor MG132 that show a unique combination of high activity and selectivity for calpains over proteasome. Tripeptide aldehydes (1-3) with an aromatic P3 substituent show enhanced activity and selectivity against ovine calpain 2 relative to chymotrypsin-like activity of proteasome. Docking studies reveal the key contacts between inhibitors and calpain to confirm the importance of the S3 pocket with respect to selectivity between calpains 1 and 2 and the proteasome.
Keywords: Calpain inhibitors; 26S proteasome inhibitors; peptidomimetics; medicinal chemistry
Rights: © 2018 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.bmc.2018.12.022
Grant ID: ARC
Appears in Collections:Aurora harvest 8
Biochemistry publications

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