ALL libraries (COBIB.SI union bibliographic/catalogue database)
-
Redox-based inactivation of cysteine cathepsins by compounds containing the 4-aminophenol moietyMirković, Bojana ...Redox cycling compounds have been reported to cause false positive inhibition of proteases in drug discovery studies. This kind of false positives can lead to unusually high hit rates in ... high-throughput screening campaigns and require further analysis to distinguish true from false positive hits. Such follow-up studies are both time and resource consuming. METHODS AND FINDINGS:In this study we show that 5-aminoquinoline-8-ol is a time-dependent inactivator of cathepsin B with a k(inact)/K(I) of 36.7 13.6 M(-1)s(-1) using enzyme kinetics. 5-Aminoquinoline-8-ol inhibited cathepsins H, L and B in the same concentration range, implying a non-specific mechanism of inhibition. Further analogues, 4-aminonaphthalene-1-ol and 4-aminophenol, also displayed time-dependent inhibition of cathepsin B with k(inact)/K(I) values of 406.4 10.8 and 36.5 1.3 M(-1)s(-1). No inactivation occurred in the absence of either the amino or the hydroxyl group, suggesting that the 4-aminophenol moiety is a prerequisite for enzyme inactivation. Induction of redox oxygen species (ROS) by 4-aminophenols in various redox environments was determined by the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate. Addition of catalase to the assay buffer significantly abrogated the ROS signal, indicating that H(2)O(2) is a component of the ROS induced by 4-aminophenols. Furthermore, using mass spectrometry, active site probe DCG-04 and isoelectric focusing we show that redox inactivation of cysteine cathepsins by 5-aminoquinoline-8-ol is active site directed and leads to the formation of sulfinic acid. CONCLUSIONS: In this study we report that compounds containing the 4-aminophenol moiety inactivate cysteine cathepsins through a redox-based mechanism and are thus likely to cause false positive hits in the screening assays for cysteine proteases.Source: PloS one [Elektronski vir]. - ISSN 1932-6203 (Vol. 6, no. 11, art. no. e27197, 2011, str. 1-11)Type of material - e-articlePublish date - 2011Language - englishCOBISS.SI-ID - 3151985
Author
Mirković, Bojana |
Sosič, Izidor |
Gobec, Stanislav, 1970- |
Kos, Janko, 1959-
Topics
katepsini |
masna spektrometrija |
4-aminofenoli
source: PloS one [Elektronski vir]. - ISSN 1932-6203 (Vol. 6, no. 11, art. no. e27197, 2011, str. 1-11)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|---|
Mirković, Bojana | 29604 |
Sosič, Izidor | 30816 |
Gobec, Stanislav, 1970- | 15284 |
Kos, Janko, 1959- | 04648 |
Source: Personal bibliographies
and: SICRIS
Select pickup location:
Material pickup by post
Delivery address:
Address is missing from the member's data.
The address retrieval service is currently unavailable, please try again.
By clicking the "OK" button, you will confirm the pickup location selected above and complete the reservation process.
By clicking the "OK" button, you will confirm the above pickup location and delivery address, and complete the reservation process.
By clicking the "OK" button, you will confirm the address selected above and complete the reservation process.
Notification
Automatic login and reservation service currently not available. You can reserve the material on the Biblos portal or try again here later.
Subject headings in COBISS General List of Subject Headings
Select pickup location
The material from the parent unit is free. If the material is delivered to the pickup location from another unit, the library may charge you for this service.
Pickup location | Material status | Reservation |
---|
Reservation in progress
Please wait a moment.
Reservation was successful.
Reservation failed.
Reservation...
Membership card:
Pickup location: