An epoxide that is oxirane in which one of the hydrogens has been replaced by a phenyl group.
ChEBI ID: 17907
There are 2 compounds belonging to this class, involving 4 studies.
| Member | Definition | Role |
|---|---|---|
| (S)-styrene-oxide | The (S)-enantiomer of styrene oxide. | |
| (R)-styrene-oxide | The (R)-enantiomer of styrene oxide. |
| Pre-1990 | 1990-2000 | 2001-2010 | 2011-2020 | Post-2020 |
|---|---|---|---|---|
| 0 | 0 | 3 | 0 | 0 |
| Article |
|---|
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
Given their medical importance, proteases have been studied by diverse approaches and screened for small molecule protease inhibitors. Here, we present a multiplexed microsphere-based protease assay that uses high-throughput flow cytometry to screen for inhibitors of the light chain protease of botulinum neurotoxin type A (BoNTALC). Our assay uses a full-length substrate and several deletion mutants screened in parallel to identify small molecule inhibitors. The use of multiplex flow cytometry has the advantage of using full-length substrates, which contain already identified distal-binding elements for the BoNTALC, and could lead to a new class of BoNTALC inhibitors. In this study, we have screened 880 off patent drugs and bioavailable compounds to identify ebselen as an in vitro inhibitor of BoNTALC. This discovery demonstrates the validity of our microsphere-based approach and illustrates its potential for high-throughput screening for inhibitors of proteases in general. |
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
Proteases regulate many biological pathways in humans and are components of several bacterial toxins. Protease studies and development of protease inhibitors do not follow a single established methodology and are mostly protease specific.. We have created recombinant fusion proteins consisting of a biotinylated attachment sequence linked to a GFP via a protease cleavage site to develop a multiplexable microsphere-based protease assay system. Using the proteases lethal factor and factor Xa, we performed kinetic experiments to determine optimal conditions for inhibitor screens and detect known inhibitors using the HyperCyt flow cytometry system.. We have demonstrated specific cleavage of lethal factor and factor Xa substrates, optimized screening conditions for these substrates, shown specific inhibition of the proteases, and demonstrated high throughput detection of these inhibitors.. The assay developed here is adaptable to any site-specific protease, compatible with high throughput flow cytometry systems, and multiplexable. Coupled with flow cytometry, which provides continuous time resolution and intrinsic resolution of free vs. bound fluorophores, this assay will be useful for high throughput screening of protease inhibitors in general and could simplify assays designed to determine protease mechanism. |