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Updated: Jan 31, 2026

Rapid One-step Enzymatic Synthesis and All-aqueous Purification of Trehalose Analogues
Published on: February 17, 2017
Tripeptide analogues of MG132 as protease inhibitors
Ashok D Pehere1, Steven Nguyen2, Sarah K Garlick3
1Department of Chemistry, and Centre for Nanoscale BioPhotonics (CNBP), University of Adelaide, Adelaide, South Australia 5005, Australia.
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.
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