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| Content Provider | Royal Society of Chemistry (RSC) |
|---|---|
| Author | Dou, Q. Ping Schmitt, Sara M. Kodanko, Jeremy J. Prakash, Jai |
| Copyright Year | 2012 |
| Abstract | Polypyridyl pentadentate ligands N4Py (1) and Bn-TPEN (2), along with their respective iron complexes, have been investigated for their ability to inhibit the purified 20S proteasome. Results demonstrated that the iron complexes of both ligands are potent inhibitors of the 20S proteasome (IC50 = 9.2 μM for [FeII(OH2)(N4Py)]2+ (3) and 4.0 μM for [FeII(OH2)(Bn-TPEN)]2+ (4)). Control experiments showed that ligand 1 or FeII alone showed no inhibition, whereas 2 was moderately active (IC50 = 96 μM), suggesting that iron, when bound to these ligands, plays a key role in proteasome inhibition. Results from time-dependent inactivation studies suggest different modes of action for the iron complexes. Time-dependent decay of proteasome activity was observed upon incubation in the presence of 4, which accelerated in the presence of DTT, suggesting reductive activation of O2 and oxidation of the 20S proteasome as a mode of action. In contrast, loss of 20S proteasome activity was not observed with 3 over time, suggesting inhibition through direct binding of the iron complex to the enzyme. Inhibition of the 20S proteasome by 4 was not blocked by reactive oxygen species scavengers, consistent with a unique oxidant being responsible for the time-dependent inhibition observed. |
| Starting Page | 174 |
| Ending Page | 178 |
| Page Count | 5 |
| File Format | HTM / HTML PDF |
| ISSN | 17565901 |
| Volume Number | 4 |
| Issue Number | 2 |
| Journal | Metallomics |
| DOI | 10.1039/c2mt00131d |
| Language | English |
| Publisher | Royal Society of Chemistry |
| Access Restriction | Open |
| Subject Keyword | Oxygen Reactive oxygen species DTT Ligand Enzyme Digital terrestrial television Direct binding IC50 Proteasome |
| Content Type | Text |
| Resource Type | Article |
| Subject | Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics |
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