Henning Jessen

Nice work by the Mayer and @jessenlab.bsky.social labs out in @elife.bsky.social. Inositol pyrophosphates regulate the vacuolar inorganic polyphosphate and Pi pools, allowing Pi to be re-imported into the cytosol when cells experience phosphate starvation. elifesciences.org/articles/108...

Establishing 18O-Labeled Inositol Phosphates for Quantitative Capillary Electrophoresis-Mass Spectrometry: Fragmentation Pathways and Comparison with 13C-Labeled Analogs Capillary electrophoresis mass spectrometry (CE-MS) allows for the rapid and accurate quantitative analysis of inositol phosphates (InsPs) and inositol pyrophosphates (PP-InsPs). The recent discovery ...

check out Guizhen´s study on 18O scrambling in the gas phase in InsPs! Establishing 18O-Labeled Inositol Phosphates for Quantitative Capillary Electrophoresis-Mass Spectrometry: Fragmentation Pathways and Comparison with 13C-Labeled Analogs | Analytical Chemistry pubs.acs.org/doi/10.1021/...

From Pharmacophore to Warhead: NAD+‐Targeting Triazoles as Mechanism‐Based Sirtuin Inhibitors We report “Sirtuin Trapping Ligands” (SirTraps), mechanism-based 1,2,3-triazole inhibitors that hijack sirtuin (SIRT) catalysis to form covalent triazolium– or triazole–ADP-ribose (ADPR) adducts from...

We call these mechanism based sirtuin inhibitors SirTraps that trap the enzyme via this ADP ribose adduct onlinelibrary.wiley.com/doi/10.1002/... 2/

Conservation of heat stress acclimation by the IPK2-type kinases that control the synthesis of the inositol pyrophosphate 4/6-InsP7 in land plants Author summary Inositol pyrophosphates (PP-InsPs) are eukaryote-specific cellular messengers that control a plethora of critical physiological processes, ranging from cellular metabolism to cellular e...

Happy to share our work on identification of non-archetypal activity of IPK2 in producing inositol pyrophosphate 4/6-IP7 and regulating heat stress acclimation-conserved in studied land plants. Grateful to @jessenlab.bsky.social for wonderful collaborative efforts!

journals.plos.org/plosgenetics...

Big congrats to Sandra for acceptance of her second paper in a row in @chemicalscience.rsc.org ! The first synthesis of monodisperse polyP10 (10 phosphate units in a row!): pubs.rsc.org/en/content/a...

Expanding the Inositol Pyrophosphate Toolbox: Stereoselective Synthesis and Application of PP‐InsP4 Isomers in Plant Signaling Inositol pyrophosphates (PP-InsPs) are highly phosphorylated signaling molecules that regulate diverse cellular processes, including phosphate homeostasis and energy metabolism across species. Despit...

congrats to Kevin! His paper on new inositol pyrophosphates is out in @angewandtechemie.bsky.social

doi.org/10.1002/anie...

because he only exhaled... must go wrong ; 12 years is quite impressive!

Congrats to Markus!! His paper on chemoenzymatic synthesis of inositol phosphates through phytate dephosphorylation is now out in @chemicalscience.rsc.org
pubs.rsc.org/en/content/a...

Congratulations to Sandra! Her paper on metal dependent endopolyphosphatase activity screens is now out in @chemicalscience.rsc.org
pubs.rsc.org/en/content/a...

📣 I will take up a Professorship at @uni-freiburg.de, Faculty of Biology. With amazing funding news coming in, we'll be in a position to establish a major research program around Epigenetics, Signaling and Synthetic Biology at the Signalhaus @cibss.bsky.social. More news and job ads to come soon!

Pools of Independently Cycling Inositol Phosphates Revealed by Pulse Labeling with 18O-Water Inositol phosphates control many central processes in eukaryotic cells including nutrient availability, growth, and motility. Kinetic resolution of a key modulator of their signaling functions, the turnover of the phosphate groups on the inositol ring, has been hampered by slow uptake, high dilution, and constraining growth conditions in radioactive pulse-labeling approaches. Here, we demonstrate a rapid (seconds to minutes) and nonradioactive labeling strategy of inositol polyphosphates through 18O-water in yeast, human cells, and amoeba, which can be applied in any media. In combination with capillary electrophoresis and mass spectrometry, 18O-water labeling simultaneously dissects the in vivo phosphate group dynamics of a broad spectrum of even rare inositol phosphates. The good temporal resolution allowed us to discover vigorous phosphate group exchanges in some inositol polyphosphates and pyrophosphates, whereas others remain remarkably inert. We propose a model in which the biosynthetic pathway of inositol polyphosphates and pyrophosphates is organized in distinct, kinetically separated pools. While transfer of compounds between those pools is slow, each pool undergoes rapid internal phosphate cycling. This might enable the pools to perform distinct signaling functions while being metabolically connected.

Happy to share Guizhen´s and Geun-Don´s analytical tour de force using 18O water labeling in combination with capillary electrophoresis
Pools of Independently Cycling Inositol Phosphates Revealed by Pulse Labeling with 18O-Water | Journal of the American Chemical Society pubs.acs.org/doi/10.1021/...

Come join my lab in @StAndrewsChem to work on this exciting project and with a fantastic team. Check out the full details on findaPhD. Please disseminate.

Peptide catalysis: Trends and opportunities Peptides are highly selective organocatalysts, with intrinsic modularity allowing precise control over structure and function. Advances in peptide synthesis, biotechnology, and cheminformatics will en...

🎉 Big day for our group: our first publication is out!
Tom did a fantastic job highlighting current trends & opportunities in peptide catalysis — now published in Chem Catalysis (open access). Huge congrats, Tom!
www.cell.com/chem-catalys...

Stereoselective chemoenzymatic phytate transformations provide access to diverse inositol phosphate derivatives Phosphorylated myo-inositols (InsPs) are essential cytoplasmic signaling molecules, while their lipidated analogs (PtdInsPs) play a crucial role in membrane signaling. Stereoselective synthesis of the...

An alternative strategy to access inositol derivatives by stereoselective dephosphorylation. Happy to share the work by Markus Haener together with @gabrielschaaf.bsky.social and many others.
chemrxiv.org/engage/chemr...

Tandem inactivation of inositol pyrophosphatases Asp1, Siw14, and Aps1 illuminates functional redundancies in inositol pyrophosphate catabolism in fission yeast | mBio Inositol pyrophosphates are key effectors of eukaryal cellular phosphate homeostasis. They are synthesized by kinases that add a β-phosphate to the 5- or 1-phosphate groups of IP6 and catabolized by t...

Very nice & complete analysis of inositol pyrophosphate catabolism by the Schwer, @jessenlab.bsky.social and Shuman labs in @mbio.bsky.social journals.asm.org/doi/10.1128/...

freiburg has some advantages when it comed to living and working

Expanding the PP-INSP₄ Toolbox: Synthesis, Stereochemical Assignment, and Application in Plant Phosphate Signaling Inositol pyrophosphates (PP-InsPs) are highly phosphorylated signaling molecules that regulate diverse cellular processes, including phosphate homeostasis and energy metabolism across species. Despite...

Happy to share Kevin´s great work on PP-InsP4 synthesis and analysis now available on Chemrxiv!

chemrxiv.org/engage/chemr...

Transport and InsP8 gating mechanisms of the human inorganic phosphate exporter XPR1 - Nature Communications The phosphate exporter XPR1 is essential for maintenance of cellular phosphate levels. Here authors present cryo-EM structures of XPR1 that reveal how binding of the signaling molecule 1,5-InsP8 to it...

please check out this wonderful paper by melinda diver and coworkers on how ip8 guards phosphate transport through xpr1

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

Biochemical and biophysical characterization of inositol-tetrakisphosphate 1-kinase inhibitors Inositol phosphates (IPs) and inositol pyrophosphate play critical roles in many biological processes as signaling molecules in pathways responsible f…

great new insights from Ji Luo, Barry O´Keefe and Brice Wilson on ITPK1 inhibitors

www.sciencedirect.com/science/arti...

Structural Insights into Broad‐Range Polyphosphate Kinase 2‐II Enzymes Applicable for Pyrimidine Nucleoside Diphosphate Synthesis This study reports the first substrate-bound structures of polyphosphate kinase 2-II (PPK2-II) enzymes, offering insights into nucleoside diphosphate (NDP) synthesis. BcPPK2 (Bacillus cereus) and LfP....

Nice work from the Andexer laboratory on PPK2 enzymes and their use in nucleotide synthesis

doi.org/10.1002/cbic...

A Screening Approach Unveils an Unknown Mn2+-dependent Endopolyphosphatase Activity in Yeast Inorganic polyphosphate (polyP) is a ubiquitous biopolymer composed of multiple orthophosphates connected by energy-rich phosphoanhydride bonds. In organisms, polyP is digested by two types of enzymes...

Hey, polyphosphate aficionados ! Here is a new screening approach by Sandra using FRET-P8 made for plate readers- she discovers a Mn ion dependent endopolyphosphatase activity in a yeast strain (quadruple KO) that was believed to be devoid of any such activity. www.biorxiv.org/content/10.1...

From Dorothea Fiedler's lab: Protein polyphosphorylation as a new post-translational modification www.biorxiv.org/content/10.1...

KIDINS220 and InsP8 safeguard the stepwise regulation of phosphate exporter XPR1

If you are interested in phosphate homeostasis and how it is regulated by XPR1, inositol pyrophosphates and KIDINS220 in concert, check out this preprint with a lot of structural information : www.biorxiv.org/content/10.1...

Proud to share our latest work with @jessenlab.bsky.social !
We optimized a method to purify polyphosphate in human cells.

The paper reviews critical steps in protocols, shares physiological insights, and yes – we’ve got NMR snapshots of mammalian polyP!
Read more: doi.org/10.1016/j.ym...
#polyP

Hi, it would be great if you can add me to the list! I am running a group in biological chemistry; here is a link to my orcid account. Thanks!
orcid.org/0000-0002-10...

For the 🧪 feed - and, honestly, the #SciArt feed. Because this belongs in a museum 😂

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Great to see our Freiburg inter-institutional (med; pharm; chem) collaborative work out: Enzymatic defluorination of a terminally monofluorinated pentyl moiety: oxidative or hydrolytic mechanism? Published in Drug Metabolism and Disposition
shorturl.at/drRW4

Our first collaborative paper in 2024 is out (led by the amazing Carsten Wagner at Unispital Zürich): The Ip6k1 and Ip6k2 Kinases Are Critical for Normal Renal Tubular Function : Journal of the American Society of Nephrology journals.lww.com/jasn/abstrac...
First version submitted in 6/21...