Esben Svenningsen
@esbensv.bsky.social
Senior Scientist with Novo Nordisk | Process Optimization and Automation
PhD in Chemical Biology from TBP lab @ Aarhus University, Denmark.
Covalent modifiers, chemoproteomics, morphological profiling / cell painting
ORCID: 0000-0001-5118-6499
PhD in Chemical Biology from TBP lab @ Aarhus University, Denmark.
Covalent modifiers, chemoproteomics, morphological profiling / cell painting
ORCID: 0000-0001-5118-6499
Absolutely welcome! Also: "bluetorial" is a much better term 🙈
November 25, 2024 at 5:37 PM
Absolutely welcome! Also: "bluetorial" is a much better term 🙈
Reposted by Esben Svenningsen
ChemBio fans please repost the #ChemicalBiology Feed bsky.app/profile/thor...
@carolynbertozzi.bsky.social @ritastrack.bsky.social @stephanhacker2.bsky.social @stuartcantrill.bsky.social @laurahowes.bsky.social @dirktrauner.bsky.social @chemjobber.bsky.social @dereklowe.bsky.social
#chemsky
@carolynbertozzi.bsky.social @ritastrack.bsky.social @stephanhacker2.bsky.social @stuartcantrill.bsky.social @laurahowes.bsky.social @dirktrauner.bsky.social @chemjobber.bsky.social @dereklowe.bsky.social
#chemsky
November 25, 2024 at 1:02 AM
Reposted by Esben Svenningsen
Great to see them apply the proteome-wide profiling method for electrophile reactivity and selectivity that we developed together with @nesvilab.bsky.social in Fragpipe in this exciting system. chemrxiv.org/engage/chemr...
Profiling the proteome-wide selectivity of diverse electrophiles
Targeted covalent inhibitors are powerful entities in drug discovery, but their application has so far mainly been limited to addressing cysteine residues. The development of cysteine-directed covalen...
chemrxiv.org
November 21, 2024 at 9:28 AM
Great to see them apply the proteome-wide profiling method for electrophile reactivity and selectivity that we developed together with @nesvilab.bsky.social in Fragpipe in this exciting system. chemrxiv.org/engage/chemr...
We will continue to develop interesting oxSTEF-chemistries for more chemoproteomics and to investigate other interesting biologies we can uncover with these new NCys probes!
Finally: Big thanks to all collaborators for their assistance in making this project become real 🙏
Finally: Big thanks to all collaborators for their assistance in making this project become real 🙏
November 20, 2024 at 3:37 PM
We will continue to develop interesting oxSTEF-chemistries for more chemoproteomics and to investigate other interesting biologies we can uncover with these new NCys probes!
Finally: Big thanks to all collaborators for their assistance in making this project become real 🙏
Finally: Big thanks to all collaborators for their assistance in making this project become real 🙏
Finally, we compared the “NCys-ome” between cells under normoxia and hypoxia. As expected, we again saw RGS4/5, but now also >10 other NCys that were seemingly regulated in their abundance or reactivity under hypoxia; only two were from known NCys-containing proteins!
November 20, 2024 at 3:37 PM
Finally, we compared the “NCys-ome” between cells under normoxia and hypoxia. As expected, we again saw RGS4/5, but now also >10 other NCys that were seemingly regulated in their abundance or reactivity under hypoxia; only two were from known NCys-containing proteins!
We then validated the probes by knocking out the NCys oxidase ADO, which should stabilise NCys-bearing proteins such as RGS4 and RGS5. Using an live-cell ABPP approach, we showed that the oxSTEF probes could indeed fish these two out!
November 20, 2024 at 3:37 PM
We then validated the probes by knocking out the NCys oxidase ADO, which should stabilise NCys-bearing proteins such as RGS4 and RGS5. Using an live-cell ABPP approach, we showed that the oxSTEF probes could indeed fish these two out!
First, we used an “unbiased” amino acid profiling workflow in FragPipe inspired by @stephanhacker2.bsky.social. We indeed found the expected NCys conjugate by open searches, and localized it to NCys using offset searches. Using oxSTEF6 we identified >800 NCys in lysates from cancer cells!
November 20, 2024 at 3:37 PM
First, we used an “unbiased” amino acid profiling workflow in FragPipe inspired by @stephanhacker2.bsky.social. We indeed found the expected NCys conjugate by open searches, and localized it to NCys using offset searches. Using oxSTEF6 we identified >800 NCys in lysates from cancer cells!
We then realized that no one had tried to use a chemical probe to fish for these – and so the idea of using the oxSTEF-probes as NCys ABPP-probes was born💡
November 20, 2024 at 3:37 PM
We then realized that no one had tried to use a chemical probe to fish for these – and so the idea of using the oxSTEF-probes as NCys ABPP-probes was born💡
At a group meeting I then asked: “Does NCys exist in live cells?” No one knew, so I went back to the office to research 📖 I found literature describing how NCys are (seemingly) uncommon but dictates protein stability (via N-degron pathways) depending on the oxidation state: Oxidation = degradation!
November 20, 2024 at 3:37 PM
At a group meeting I then asked: “Does NCys exist in live cells?” No one knew, so I went back to the office to research 📖 I found literature describing how NCys are (seemingly) uncommon but dictates protein stability (via N-degron pathways) depending on the oxidation state: Oxidation = degradation!
Background: We previously developed the oxSTEF probes for disulphide rebridging in bioconjugation contexts. The probes feature two sulfur-based leaving groups which can exchange for other nucleophiles. Interestingly, with calcitonin we observed quite good NCys reactivity and selectivity.
November 20, 2024 at 3:37 PM
Background: We previously developed the oxSTEF probes for disulphide rebridging in bioconjugation contexts. The probes feature two sulfur-based leaving groups which can exchange for other nucleophiles. Interestingly, with calcitonin we observed quite good NCys reactivity and selectivity.