New peptidomimetic boronates for selective inhibition of the chymotrypsin-like activity of the 26S proteasome

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dc.contributor.authorZhang, X.
dc.contributor.authorAdwal, A.
dc.contributor.authorTurner, A.
dc.contributor.authorCallen, D.
dc.contributor.authorAbell, A.
dc.date.issued2016
dc.descriptionPublication Date (Web): September 13, 2016
dc.description.abstractProteasome is a large proteinase complex that degrades proteins via its three catalytic activities. Among these activities, the “chymotrypsin-like” activity has emerged as the focus of drug discovery in cancer therapy. Here, we report new peptidomimetic boronates that are highly specific for the chymotrypsin-like catalytic activity of the proteasome. These new specific proteasome inhibitors were demonstrated to have higher in vitro potency and selective cytotoxicity for cancer cells compared to benchmark proteasome inhibitors: bortezomib and carfilzomib. In breast cancer cell lines, treatment with 1a or 2a induced accumulation of the high molecular weight polyubiqutinated proteins at similar levels observed for bortezomib and carfilzomib, indicating that cancer cell death caused by 1a/2a is chiefly due to proteasome inhibition.
dc.description.statementofresponsibilityXiaozhou Zhang, Alaknanda Adwal, Andrew G. Turner, David F. Callen, and Andrew D. Abell
dc.identifier.citationACS Medicinal Chemistry Letters, 2016; 7(12):1039-1043
dc.identifier.doi10.1021/acsmedchemlett.6b00217
dc.identifier.issn1948-5875
dc.identifier.issn1948-5875
dc.identifier.orcidAdwal, A. [0000-0001-9441-5407]
dc.identifier.orcidCallen, D. [0000-0002-6189-9991]
dc.identifier.orcidAbell, A. [0000-0002-0604-2629]
dc.identifier.urihttp://hdl.handle.net/2440/102417
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.relation.grantARC
dc.rights© American Chemical Society
dc.source.urihttps://doi.org/10.1021/acsmedchemlett.6b00217
dc.subject26S proteasome inhibitors; boronic ester; chymotrypsin-like activity; immunoproteasome; solid cancer
dc.titleNew peptidomimetic boronates for selective inhibition of the chymotrypsin-like activity of the 26S proteasome
dc.typeJournal article
pubs.publication-statusPublished

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