Tripeptide analogues of MG132 as protease inhibitors.
Pehere AD, Nguyen S, Garlick SK, Wilson DW, Hudson I, Sykes MJ, Morton JD, Abell AD Department of Chemistry, and Centre for Nanoscale BioPhotonics (CNBP), University of Adelaide, Adelaide, South Australia 5005, Australia. Electronic address: [email protected]
Share
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.
This website was developed with the generous support of a donor.
Burnet Institute (Australia) is located on the traditional land of the Boon Wurrung people and we offer our respects to their Elders past and present. We recognise and respect the continuation of cultural, spiritual and educational practices of Aboriginal and Torres Strait Islander peoples of this land.
Oops!
It looks like something may have gone wrong, and some of the resources required to load the page may not have loaded correctly.
