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

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...

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...

MiBIG 4.0 is online!

#secmet #BGC #mibig #microsky

academic.oup.com/nar/advance-...

In a new preprint @chemrxiv.bsky.social, work from @bgless.bsky.social and Sabrina Schmied investigate the mechanism of a rearrangement that can lead to peptide/protein backbone cleavage.

Thanks to #LEOFondet for funding the project that led to this discovery.

chemrxiv.org/engage/chemr...

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

Little Reminder: tomorrow 2pm. We are excited 😉

Opportunity in chemical biology & #proteomics at Pfizer (Groton CT USA) ref: 4924293 | closing: 06-Dec-2024 #ChemBiol #biochem #chemsky 🧪
pfizer.wd1.myworkdayjobs.com/PfizerCareer...

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

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

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

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, 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!

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💡

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.

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