Modular Vinyl Phosphonamidates for Cysteine-Directed Protein Targeting Covalent inhibitors and chemical probes targeting ligandable cysteine residues have emerged as powerful tools for drug discovery and proteomics. In this study, we introduce vinyl phosphonamidates (VPA...

I am excited to share that our manuscript on vinyl phosphonamidates (VPAs) as latent electrophiles for cysteine targeting has just been published in the Journal of the American Chemical Society.

doi.org/10.1021/jacs...

Thanks to my great colleagues who help me shape this project!

This project originated from the thesis of my exceptionally talented student Charlotte Völkel. It was a true pleasure to collaborate with this multi-disciplinary team to advance this project.

Moreover, their modular architecture allows the installation of additional functionality directly at the electrophilic center, a unique property we utilized to develop alkyne-based probes and covalent PROTACs.

Modular Vinyl Phosphonamidates for Cysteine-Directed Protein Targeting Covalent inhibitors and chemical probes targeting ligandable cysteine residues have emerged as powerful tools for drug discovery and proteomics. In this study, we introduce vinyl phosphonamidates (VPA...

While VPAs show barely any reactivity toward glutathione under physiological conditions, incorporating them into kinase-targeting ligands enables robust covalent engagement of the target proteins and show significantly improved selectivity while maintaining inhibitory efficacy.

🎉 Excited to share the first bioRxiv & medRxiv preprint from my PostDoc.
It’s been — and continues to be — an incredible journey into the world of epigenetics, exploring how we can reprogram oncogenic transcription factor activity using chemical inducers of proximity.
👨‍🔬🧪🧬🧫

Targeted Transcriptional Repression by Induced Proximity Most cancer driving proteins remain undruggable due to the absence of ligandable pockets and their reliance on intrinsically disordered or protein-DNA/protein-protein interactions. Transcription facto...

We unveil TRACERs, Transcriptional Regulation via Active Control of Epigenetic Reprogramming: a new small-molecule-based induced-proximity modality that silences transcription factors by recruiting endogenous corepressor complexes for locus-specific repression.
www.biorxiv.org/content/10.1...

The Vienna BioCenter PhD Program application deadline is approaching: October 10!

Join one of Europe’s premier life science campuses, home to cutting-edge research across all areas of biology.
Apply and start your scientific journey in Vienna!

training.vbc.ac.at/phd-program/

#PhD #LifeSciences

Nucleoside diphosphate kinase A (NME1) catalyses its own oligophosphorylation - Nature Chemistry Our understanding of how post-translational modification—protein phosphorylation—impacts the complexity of eukaryotic signalling pathways is continuously expanding. Now, protein oligophosphorylation h...

Brace yourselves! Arif from the Fiedler lab discovered+characterized in collaboration with us & other groups within the @fmp-berlin.de a novel PTM: autocatalytic oligophosphorylation (up to 6 Phosphates 😲). Still mysterious in origin, function & regulation.

www.nature.com/articles/s41...

If you are already using FragPipe, the open search might help. In case there is some loss/water addition/sodium addicts caused by your modification.
Also, how sure are you that the modification is stable under acidic conditions?

Was really fun working with you on that project! 😃

Interesting talk by Mark de Geus at #Lunteren. He talked about his work on incorporating aryl thiols into proteins and exploring, if they can be labeled selectively over cysteine residues. Cool applications to site-selective protein labeling.

My write-up on this, if it’s of any use or interest: nanoscale.blogspot.com/2025/02/indi...

To my friends and colleagues at UAB, IU, UF, FSU, UL, WashU, OSU, CWRU, etc, etc. Call both your senators and your representative. They listen. Emphasize the direct economic impact of NIH research, and the indirect impacts on pharmaceutical/biotech. Underscore its relevance to national security.

‼️PhD Position in Chemical Biology at the University Antwerp‼️#chembio

✔️Deadline: ‼️February 20, 2025‼️
✔️Find full details and submit your application here: www.uantwerpen.be/en/jobs/vaca...

Extensive protein pyrophosphorylation revealed in human cell lines - Nature Chemical Biology www.nature.com/artic...

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#proteomics #prot-paper

This shows that our reviewing process does not work at all…