85157-21-7Relevant articles and documents
A Suite of Activity-Based Probes to Dissect the KLK Activome in Drug-Resistant Prostate Cancer
Bakker, Alexander T.,Bevan, Charlotte L.,Bock, Nathalie,Clements, Judith A.,De Vita, Elena,Engelsberger, Elisabeth,Kryza, Thomas,Lovell, Scott,Maneiro, Maria,Neodo, Anna,Tanaka, Reiko J.,Tate, Edward W.,Williams, Elizabeth D.,Xu, Congyi,Zhang, Leran
supporting information, p. 8911 - 8924 (2021/06/28)
Kallikrein-related peptidases (KLKs) are a family of secreted serine proteases, which form a network (the KLK activome) with an important role in proteolysis and signaling. In prostate cancer (PCa), increased KLK activity promotes tumor growth and metastasis through multiple biochemical pathways, and specific quantification and tracking of changes in the KLK activome could contribute to validation of KLKs as potential drug targets. Herein we report a technology platform based on novel activity-based probes (ABPs) and inhibitors enabling simultaneous orthogonal analysis of KLK2, KLK3, and KLK14 activity in hormone-responsive PCa cell lines and tumor homogenates. Importantly, we identifed a significant decoupling of KLK activity and abundance and suggest that KLK proteolysis should be considered as an additional parameter, along with the PSA blood test, for accurate PCa diagnosis and monitoring. Using selective inhibitors and multiplexed fluorescent activity-based protein profiling (ABPP), we dissect the KLK activome in PCa cells and show that increased KLK14 activity leads to a migratory phenotype. Furthermore, using biotinylated ABPs, we show that active KLK molecules are secreted into the bone microenvironment by PCa cells following stimulation by osteoblasts suggesting KLK-mediated signaling mechanisms could contribute to PCa metastasis to bone. Together our findings show that ABPP is a powerful approach to dissect dysregulation of the KLK activome as a promising and previously underappreciated therapeutic target in advanced PCa.
Ubiquitin 7-amino-4-carbamoylmethylcoumarin as an improved fluorogenic substrate for deubiquitinating enzymes
Li, Yi-Tong,Huang, Yi-Chao,Xu, Yang,Pan, Man,Li, Yi-Ming
, p. 4085 - 4090 (2016/07/06)
A new fluorogenic substrate Ub-ACC (ubiquitin C-terminal 7-amino-4-carbamoylmethyl-coumarin) was developed for DUB (deubiquitinating enzyme) activity assays. This substrate can be synthesized with higher efficiency than the classical DUB substrate, Ub-AMC (ubiquitin C-terminal 7-amino-4-methylcoumarin). DUB assays using UCH-L3, OTUD2 and USP30 demonstrated that Ub-ACC shows nearly 2-fold higher sensitivity than Ub-AMC.
O-fluorination of aromatic azides yields improved azido-based fluorescent probes for hydrogen sulfide: Synthesis, spectra, and bioimaging
Wei, Chao,Wang, Runyu,Wei, Lv,Cheng, Longhuai,Li, Zhifei,Xi, Zhen,Yi, Long
supporting information, p. 3586 - 3592 (2015/02/05)
Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule with multiple biological functions. To visualize the endogenous in situ production of H2S in real time, new coumarin- and boron-dipyrromethene- based fluorescent turn-on probes were developed for fast sensing of H2S in aqueous buffer and in living cells. Introduction of a fluoro group in the ortho position of the aromatic azide can lead to a greater than twofold increase in the rate of reaction with H2S. On the basis of o-fluorinated aromatic azides, fluorescent probes with high sensitivity and selectivity toward H2S over other biologically relevant species were designed and synthesized. The probes can be used to in situ to visualize exogenous H2S and d-cysteine-dependent endogenously produced H2S in living cells, which makes them promising tools for potential applications in H2S biology.
