iiinova — where your digital self keeps evolving

Reposted by Esben Svenningsen

Anders Kiib @aekiib.bsky.social · 30/01/2025

I am excited to share that the latest project from the @tbpoulsen.bsky.social group, detailing the syntheses and biological evaluation of the four natural products cyclohelminthol I-IV is now available in Chemical Science! doi.org/10.1039/D4SC... A short "Bluetorial" below #ChemSky #ChemBio 1/7

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Reposted by Esben Svenningsen

Jacob Corn @jcornlab.bsky.social · 30/01/2025

Cells are filled with toxic stuff that damages healthy proteins. Is that garbage just left to rot on the curb? No way! Ubiquitin ligases have evolved to recognize chemical damage and clean it up! www.nature.com/articles/s41...

nature.com

C-terminal amides mark proteins for degradation via SCF–FBXO31 - Nature

SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

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Reposted by Esben Svenningsen

Thomas Tørring @thomastorring.bsky.social · 22/12/2024

A Christmas present to all of the lasso peptide connoisseurs out there. The next chapter in our work is on triculamin is ready on bioRxiv. Great work by two incredibly talented graduate students @amerrild.bsky.social and @tizianasvenningsen.bsky.social. www.biorxiv.org/content/10.1...

biorxiv.org

Convergent Evolution of the Antimycobacterial Lasso Peptide Triculamin

Triculamin is a ribosomally synthesized and post-translationally modified peptide (RiPP) lasso peptide with potent antimycobacterial activity, produced by an unusual, non-canonical biosynthetic gene c...

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Reposted by Esben Svenningsen

Sascha Hoogendoorn @hoogendoornlab.bsky.social · 03/12/2024

Job alert: fully funded postdoc position in chemical biology in beautiful Geneva! Do you have a PhD in Chemical Biology or related field with organic synthetic experience? Apply now! Details on how to apply can be found here: www.hoogendoornlab.org/joinus #chemsky #ChemBio

hoogendoornlab.org

Join us! | Hoogendoorn Lab

Openings for PhD students and postdocs will be advertized here

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Reposted by Esben Svenningsen

NFDI4Chem @nfdi4chem.de · 28/11/2024

Little Reminder: tomorrow 2pm. We are excited 😉

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Reposted by Esben Svenningsen

Yamuna Krishnan @krishnanyamuna.bsky.social · 26/11/2024

I want to write a paper titled “the sky is blue, the ocean is deep and trees are green”

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Esben Svenningsen @esbensv.bsky.social · 25/11/2024

Absolutely welcome! Also: "bluetorial" is a much better term 🙈

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Esben Svenningsen @esbensv.bsky.social · 20/11/2024

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 🙏

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Esben Svenningsen @esbensv.bsky.social · 20/11/2024

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!

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Esben Svenningsen @esbensv.bsky.social · 20/11/2024

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!

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Esben Svenningsen @esbensv.bsky.social · 20/11/2024

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!

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Esben Svenningsen @esbensv.bsky.social · 20/11/2024

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💡

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Esben Svenningsen @esbensv.bsky.social · 20/11/2024

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!

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Esben Svenningsen @esbensv.bsky.social · 20/11/2024

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.

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Esben Svenningsen @esbensv.bsky.social · 20/11/2024

In my first #bsky post, I am very happy and proud to share the new(ish) preprint of my post doc project on N-terminal cysteine (NCys) chemoprotomics using the oxSTEF probes! Preprint at 👉 www.doi.org/10.26434/chemrxiv-2024-4w549 Skeeturial (??) below ⬇️ #ChemSky #ChemBio

Graphical abstract of scientific paper. Chemical structures of oxSTEF probes and N-terminal cysteine, showing their reaction followed by a schematic of a proteomics experiment

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