Work

New Peptidomimetic Boronates for Selective Inhibition of the Chymotrypsin-like Activity of the 26S Proteasome

Year: 2016

Type: article

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.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.6b00217

Authors: Xiaozhou Zhang, Alaknanda Adwal, Andrew G. Turner, David F. Callen, Andrew D. Abell

Institutions: The University of Adelaide, ARC Centre for Nanoscale BioPhotonics

Language: English

Topic: Ubiquitin and proteasome pathways

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Australian National Fabrication Facility, U.S. Food and Drug Administration, Australian Research Council