Journal article
Application of a Sulfoxonium Ylide Electrophile to Generate Cathepsin X-Selective Activity-Based Probes
SJ Mountford, BM Anderson, B Xu, ESV Tay, M Szabo, ML Hoang, J Diao, L Aurelio, RI Campden, E Lindström, EK Sloan, RM Yates, NW Bunnett, PE Thompson, LE Edgington-Mitchell
ACS Chemical Biology | AMER CHEMICAL SOC | Published : 2020
Abstract
Cathepsin X/Z/P is cysteine cathepsin with unique carboxypeptidase activity. Its expression is associated with cancer and neurodegenerative diseases, although its roles during normal physiology are still poorly understood. Advances in our understanding of its function have been hindered by a lack of available tools that can specifically measure the proteolytic activity of cathepsin X. We present a series of activity-based probes that incorporate a sulfoxonium ylide warhead, which exhibit improved specificity for cathepsin X compared to previously reported probes. We apply these probes to detect cathepsin X activity in cell and tissue lysates, in live cells and in vivo, and to localize active..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank C. Nowell for maintaining the imaging facilities at the Monash Institute of Pharmaceutical Sciences. MDA-MB231HM cells were a kind gift from Z. Ou, Fudan University, Shanghai Cancer Center. L.E.M. was supported by an Early Career Fellowship from the National Health and Medical Research Council of Australia (NHMRC, GNT1091636), a Grimwade Fellowship funded by the Russell and Mab Grimwade Miegunyah Fund at the University of Melbourne, a DECRA Fellowship from the Australian Research Council (ARC, DE180100418), and by seed grants from Monash University. N.W.B. was supported by grants from the National Institutes of Health (NS102722, DE026806, DK118971) and the United States Department of Defense (W81XWH1810431).