Activity-Based Probes for the High Temperature Requirement A Serine Proteases.
Ho Yeon NamDasom SongJinny EoNa-Eun ChoiJong-Ah HongKyung Tae HongJun-Seok LeeJiwon SeoJiyoun LeePublished in: ACS chemical biology (2020)
The high temperature requirement A (HTRA) family of serine proteases mediates protein quality control. These proteins process misfolded proteins in several diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). While their structures and activation mechanisms have been studied, the precise details of the regulation of their activity under physiological conditions have not been completely elucidated, partly due to the lack of suitable chemical probes. In the present study, we developed novel activity-based probes (ABPs) targeting the HTRAs and demonstrated their utility in the monitoring and quantification of changes in enzyme activity in live cells. Using our probes, we found the activity of HTRA1 to be highly elevated in an AD-like cell-based model. We also observed the active HTRA2 in live cells by using a mitochondrion-targeted probe. We believe that our probes can serve as a useful tool to study the role of human HTRAs in neurodegenerative diseases.
Keyphrases
- high temperature
- living cells
- small molecule
- fluorescence imaging
- induced apoptosis
- single molecule
- quality control
- endothelial cells
- cell cycle arrest
- protein protein
- cancer therapy
- oxidative stress
- endoplasmic reticulum stress
- cognitive decline
- single cell
- mesenchymal stem cells
- quantum dots
- drug delivery
- cell proliferation