Philippe Pourquier

[Nature] Indole | benzofuran —> indazole & benzimidazole | benzoisoxazole & benzoxazole This work (Studer lab, Münster U) presents a novel skeletal editing strategy where indoles and benzofurans can be transformed into the corresponding indazoles and benzoisoxazoles via oxidative cleavage of the C2/C3 double bond to form an oxime. Activation of the oxime –OH followed by ring closure/LG displacement then yields the indazole or benzoisoxazole analog. On the other hand, the same activated oxime intermediate can also undergo dehydration to form a nitrilium cation that then undergoes intramolecular cyclization to give either the benzimidazole or benzoxazole. The reaction was found to have a good functional group tolerance for both the skeletal editing of indoles and benzofurans, with the benzofurans generally giving a higher efficiency in the radical-mediated oxidative cleavage process compared to the indoles. Complex biactive molecules were also amenable to this skeletal editing protocol and through the use of 15N-radiolabelled N-nitrosomorpholine (synthesized from commercially available 15N-radiolabelled NaNO2), the corresponding 15N-labelled indazole could also be accessed. The ability to modify and synthesize medchem-relevant heterocycles in a mild 1-pot manner at a late stage instead of having to remake them from scratch is definitely very convenient in drug discovery campaigns. Definitely will be keeping up to date on new developments in this exciting area ! Check it out here: Title: C-to-N atom swapping and skeletal editing in indoles and benzofurans Authors: Zhe Wang, Pengwei Xu, Shu-Min Guo, Constantin G. Daniliuc & Armido Studer https://lnkd.in/gX7QX5iX

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𝐭𝐢𝐦𝐒𝐡𝐢𝐟𝐭 — 𝐒𝐨𝐥𝐯𝐢𝐧𝐠 𝐭𝐡𝐞 𝐜𝐨𝐦𝐩𝐥𝐞𝐱𝐢𝐭𝐲 𝐨𝐟 𝐭𝐡𝐞 𝐫𝐞𝐚𝐜𝐭𝐢𝐯𝐞 𝐩𝐫𝐨𝐭𝐞𝐨𝐦𝐞 𝐢𝐧 𝐭𝐡𝐞 𝐠𝐚𝐬 𝐩𝐡𝐚𝐬𝐞 A team led by Peter Bellotti and Jacob Geri from Cornell University has introduced timShift, a gas-phase separation strategy that enables direct detection of modified peptides using #timsTOF — without the need for traditional, costly and slow enrichment steps. 𝐖𝐡𝐲 𝐭𝐡𝐢𝐬 𝐦𝐚𝐭𝐭𝐞𝐫𝐬 Activity-Based Protein Profiling (ABPP) helps us understand how proteins behave in real time — how they respond to drugs, stress, e.g., in diseases. It’s a powerful way to discover new drug targets and understand biology at the molecular level. But here’s the challenge: proteomic samples are chemically massive — hundreds of thousands of peptides, only a tiny fraction of which are modified and relevant. Traditional workflows rely on liquid-phase enrichment (e.g., streptavidin/biotin), which are complex, loss-prone, slow and require large sample inputs. 𝐭𝐢𝐦𝐒𝐡𝐢𝐟𝐭 𝐟𝐮𝐧𝐝𝐚𝐦𝐞𝐧𝐭𝐚𝐥𝐥𝐲 𝐜𝐡𝐚𝐧𝐠𝐞𝐬 𝐭𝐡𝐞 𝐠𝐚𝐦𝐞 • Uses a dicationic, cysteine-reactive probe to shift ion mobility • Physically separates modified peptides within milliseconds inside the timsTOF • Enables highly selective identification and quantification of labeled peptides • Profiles >8,200 reactive cysteine sites with 25× less input • Compatible with 96-well high-throughput and low-input formats (as few as 20,000 cells) 𝐖𝐡𝐲 𝐓𝐈𝐌𝐒 𝐢𝐬 𝐤𝐞𝐲 Trapped Ion Mobility Spectrometry (TIMS) adds a new dimension of separation (4D-proteomics) — allowing modified peptides to be isolated in the gas phase with high resolution and speed. This unlocks new possibilities for low-input, high-throughput, and streamlined ABPP workflows and beyond... #StayCurious Full paper: https://lnkd.in/gmdc7fJy #proteomics #massspectrometry #ABPP #chemicalbiology #timsTOF #timShift #drugdiscovery #cysteineprofiling #ionmobility

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[Part 5/6] – The False Choice Between Suspension and Scalability There’s a persistent myth in bioprocessing: “If you want to scale, you have to go suspension.” But scalability is not a property of the cell. It’s a property of the system. The real questions are: - How many cells per liter can a system provide? - How much manual work is required per batch? - How predictable is your output - across runs and operators? Modern adherent systems can: - Increase facility output by 10–20x at the same footprint - Reduce operator time by up to 98% (with automation) - Achieve high cell quality and batch consistency And they let you stay closer to the native biology, which means fewer surprises downstream. So no, you don’t have to go to suspension. You just need to stop using 1990s tools for 2025 problems. ➡️ Want to go even deeper? I’ll close this series with one final thought in Part 6.

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🌟 Epigenetics: The Science Beyond DNA 🌟 We often think of DNA as a fixed code — an unchangeable script that defines who we are. But modern science reveals a fascinating truth: while our genetic code stays constant, its expression can be dynamically regulated. This regulation is called epigenetics. 🧬 🔬 How does it work? Epigenetic mechanisms act like switches and dimmers for our genes: DNA Methylation ➝ Addition of methyl groups can “tag” DNA, silencing or activating genes without changing the sequence. Histone Modification ➝ Histone proteins wrap DNA. Epigenetic factors can modify histone “tails,” making genes either tightly packed (inactive) or loosely open (active). 🌍 What influences epigenetics? Epigenetic marks are not random — they are shaped by developmental stages, diet, aging, pharmaceuticals, and environmental exposures. In essence, our genes interact with the world around us. ⚠️ Why does it matter? Altered epigenetic patterns are strongly linked to major health outcomes, including: ✔️ Cancer ✔️ Autoimmune diseases ✔️ Mental disorders ✔️ Diabetes 💡 The Bigger Picture Epigenetics teaches us that health is not only inherited — it’s also influenced. This insight is transforming precision medicine, drug development, and preventive healthcare. It empowers us with the understanding that while we cannot rewrite our genetic code, we can influence how it is read. 🔖 We don’t just carry our genes; we carry the ability to shape their expression. #Epigenetics #MolecularBiology #LifeSciences #PersonalizedMedicine #HealthcareInnovation #FutureOfMedicine

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