Uncategorized

My colleagues from The Structural Genomics Consortium (SGC) (Rezart Zhubi, Andreas C. Joerger, Stefan Knapp) just published a paper “𝐒𝐭𝐫𝐮𝐜𝐭𝐮𝐫𝐚𝐥 𝐚𝐧𝐚𝐥𝐲𝐬𝐢𝐬 𝐨𝐟 𝐓𝐑𝐈𝐌 𝐟𝐚𝐦𝐢𝐥𝐲 𝐏𝐑𝐘𝐒𝐏𝐑𝐘 𝐝𝐨𝐦𝐚𝐢𝐧𝐬 𝐚𝐧𝐝 𝐢𝐭𝐬 𝐢𝐦𝐩𝐥𝐢𝐜𝐚𝐭𝐢𝐨𝐧𝐬 𝐟𝐨𝐫 𝐄3-𝐥𝐢𝐠𝐚𝐧𝐝 𝐝𝐞𝐬𝐢𝐠𝐧” that discusses 9 new X-ray structures, providing valuable structural insights for this family of E3 ligases. 🔑 Key Structural Findings:✅ Conserved β-sandwich fold…

DNA methyltransferases (MTases) can recognize specific DNA sequences and transfer a methyl group from the S-adenosyl-L-methionine (SAM) cofactor to a target nucleobase. This ability has been exploited for sequence-specific DNA labeling using synthetic SAM analogues (SMILing, mTAG). However, both approaches (SMILing and mTAG) share following limitations:🔸 The SAM analogues are chemically reactive (labile aziridine rings…

Researchers from The Chinese University of Hong Kong discovered an alternative mechanism in which organo-selenium acts as a C-H hydrogen bond catalyst, enabling (not only) halogenation of arenes. Key highlights✔️ reveals a previously unexplored mechanism✔️ enables efficient electrophilic halogenation with low catalyst loadings✔️ applicable to the late-stage bromination of several drug molecules✔️ organo-catalyst 2c can…

Finding potent small-molecule E3 ligase binders is notoriously tough. Here’s how teams from AstraZeneca, Pharmaron, and X‑Chem collaborated to overcome this challenge and discover a drug‑like ligand for the CHIP/STUB1 protein. Key highlights 🔬 Background and Significance– STUB1/CHIP is a U-box E3 ubiquitin ligase that targets misfolded proteins via interactions with Hsc70/Hsp90.– The currently known…

Induced proximity is more than ubiquitination and targeted protein degradation. In the recent literature we have seen proximity-inducing modalities for phosphorylation and dephosphorylation, deubiquitination, glycosylation and more. 𝗖𝘂𝗿𝗿𝗲𝗻𝘁 𝗹𝗶𝗺𝗶𝘁𝗮𝘁𝗶𝗼𝗻However, when we induce proximity between our protein of interest (POI) and an effector protein, it can be counterproductive to use inhibitory ligands for recruitment of the…

 The number of spirocyclic-N-heterocycles has increased dramatically in the recent years. From 10,000 in 2023 ➡️ 90,000 in 2025 (Substructure search on Reaxys). Functionalized spirocycles are highly valuable synthetic building blocks, especially in medicinal chemistry. 💊 However, if you want to decorate them a little bit more, you are likely tapping into the chemical space…

Imagine a scaffold hopping strategy where you don’t have to re-design your synthetic route for each scaffold. You don’t need Jedi tricks nor power of the dark side to achieve that. This has been addressed for 4-arylpyrimidines in a recent publication by Shun Li et al. published in Nature Communications: “Skeletal editing of 4-arylpyrimidines into…

The microcosmos of biological processes is complex and full of surprises. This is also the case for a new preprint from Richert, Nůsková et al. While developing rabeprazole-thalidomide hybrids as targeted protein degraders, the authors observed rapid, reversible ATP depletion in cells. Surprisingly, this effect was attributed to PROTAC molecules with a certain molecular structure. 𝗠𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝗺Mechanistic…

Do you like to Smile? Or perhaps you’re a fan of rearrangement reactions like me? If so, you’ll want to check out this new paper from my former colleague, Srimanta Manna, Ph.D., and his team: “N,N-Disubstituted Anilines Synthesis through Smiles Rearrangement“ 💡 Why it matters:This methodology enables metal-free C–N coupling under mild conditions, and offers…

Recently published paper in Nature Communications claims (as the title says): “General method for carbon–heteroatom cross-coupling reactions via semiheterogeneous red-light metallaphotocatalysis” Quite a bold statement, so let’ take a look at it. Key highlights include: ✅ Red light penetrates 23x deeper than blue light – enabling gram-scale reactions in 10 cm flasks ✅ Four bond…