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Type: Journal article
Title: New peptidomimetic boronates for selective inhibition of the chymotrypsin-like activity of the 26S proteasome
Author: Zhang, X.
Adwal, A.
Turner, A.
Callen, D.
Abell, A.
Citation: ACS Medicinal Chemistry Letters, 2016; 7(12):1039-1043
Publisher: American Chemical Society
Issue Date: 2016
ISSN: 1948-5875
Statement of
Xiaozhou Zhang, Alaknanda Adwal, Andrew G. Turner, David F. Callen, and Andrew D. Abell
Abstract: Proteasome 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.
Keywords: 26S proteasome inhibitors; boronic ester; chymotrypsin-like activity; immunoproteasome; solid cancer
Description: Publication Date (Web): September 13, 2016
Rights: © American Chemical Society
RMID: 0030057656
DOI: 10.1021/acsmedchemlett.6b00217
Appears in Collections:Medical Sciences publications

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