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https://hdl.handle.net/2440/118429
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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 1464-3391 |
Statement of Responsibility: | 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 |
Published version: | http://dx.doi.org/10.1016/j.bmc.2018.12.022 |
Appears in Collections: | Aurora harvest 8 Biochemistry publications |
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