Journal article
Evaluation of a dithiocarbamate derivative as an inhibitor of human glutaredoxin-1
Journal of Enzyme Inhibition and Medicinal Chemistry, Vol.28(3), pp.456-462
2013
Abstract
Context: Glutaredoxins (GRX) are involved in the regulation of thiol redox state. GRX-1 is a cytosolic enzyme responsible for the catalysis of deglutathionylation of proteins. To date, very few inhibitors of GRX-1 have been reported.
Objective: The objective of this paper is to report 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethyl-sulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as an inhibitor of human GRX-1.
Materials and methods: The mechanism of inhibition of GRX-1 was investigated using dialysis, substrate protection, and mass spectrometry.
Results: 2-AAPA inhibits GRX-1 in a time and concentration dependent manner. The activity did not return following dialysis indicating that inhibition is irreversible. Results of substrate protection and mass spectrometry indicate that the inhibition is occurring at the active site. The compound also produced GRX inhibition in human ovarian cancer cells.
Discussion: 2-AAPA is an irreversible GRX-1 inhibitor with similar or greater potency compared to previously reported inhibitors.
Conclusion: The inhibition of GRX-1 by 2-AAPA could be used as a tool to study thiol redox state.
Details
- Title
- Evaluation of a dithiocarbamate derivative as an inhibitor of human glutaredoxin-1
- Authors/Creators
- S.S. Sadhu (Author/Creator) - South Dakota State UniversityE. Callegari (Author/Creator) - University of South DakotaY. Zhao (Author/Creator) - Michigan State UniversityX. Guan (Author/Creator) - South Dakota State UniversityT. Seefeldt (Author/Creator) - South Dakota State University
- Publication Details
- Journal of Enzyme Inhibition and Medicinal Chemistry, Vol.28(3), pp.456-462
- Publisher
- Taylor & Francis
- Identifiers
- 991005541850407891
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
23 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.127 Molecular & Cell Biology - Pharmacology
- 1.127.973 Thiol-Disulfide Systems
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Medicinal
- ESI research areas
- Biology & Biochemistry