Uncategorized

Wang et al. report a new copper-catalyzed methodology for C(sp³)-N cross-coupling of unactivated alkyl halides with diverse nucleophiles under thermal conditions (JACS): “𝘈 𝘎𝘦𝘯𝘦𝘳𝘢𝘭 𝘊𝘰𝘱𝘱𝘦𝘳-𝘊𝘢𝘵𝘢𝘭𝘺𝘻𝘦𝘥 𝘙𝘢𝘥𝘪𝘤𝘢𝘭 𝘊𝘳𝘰𝘴𝘴-𝘊𝘰𝘶𝘱𝘭𝘪𝘯𝘨 𝘰𝘧 𝘜𝘯𝘢𝘤𝘵𝘪𝘷𝘢𝘵𝘦𝘥 𝘈𝘭𝘬𝘺𝘭 𝘏𝘢𝘭𝘪𝘥𝘦𝘴” (Colleagues doing automated or high-throughput synthesis will love this) Key InnovationThe success of this methodology relies on the use of anionic N,N,N-ligands to enhance…

Then I would like to invite you to read our paper in RSC Chem. Biol. which also represents my first corresponding authorship: “𝘋𝘪𝘴𝘤𝘰𝘷𝘦𝘳𝘺 𝘰𝘧 𝘢𝘯 𝘦𝘹𝘲𝘶𝘪𝘴𝘪𝘵𝘦𝘭𝘺 𝘴𝘦𝘭𝘦𝘤𝘵𝘪𝘷𝘦 𝘞𝘋𝘙5 𝘤𝘩𝘦𝘮𝘪𝘤𝘢𝘭 𝘱𝘳𝘰𝘣𝘦 𝘢𝘤𝘤𝘦𝘭𝘦𝘳𝘢𝘵𝘦𝘥 𝘣𝘺 𝘢 𝘩𝘪𝘨𝘩-𝘲𝘶𝘢𝘭𝘪𝘵𝘺 𝘋𝘌𝘓–𝘔𝘓 𝘏𝘪𝘵” (DEL-ML = DNA Encoded Library + Machine Learning) Highlights✅ We demonstrate power of DEL-ML and how it can accelerate…

For decades, creating proteins with extended backbones (β, γ, δ-amino acids) inside living cells has been challenging. Researchers at University of California, Berkeley (Alanna Schepartz, Leah Roe), Yale University, Amgen and collaborators developed BEAR reactions to address this challenge. 𝐖𝐡𝐲 𝐝𝐨𝐞𝐬 𝐭𝐡𝐢𝐬 𝐦𝐚𝐭𝐭𝐞𝐫?→ Extension of backbone can lead to improved phys-chem properties→ Better stability and resistance to…

🔸 50 new CRBN neosubstrates🔸 3 bona fide degraders🔸 MS-proteomic platform expanding druggable proteome All of this packed in single paper❗ by colleagues from NEOsphere Biotechnologies GmbH, ICR Centre for Protein Degradation and St. Jude Children’s Research Hospital – ALSAC Additional highlights✅ Screened 100 CRBN-binders across two cancer cell lines✅ Identified 50 novel CRBN neosubstrates❗✅…

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…