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How do you study the 90% of proteins that lack small-molecule binding partners? By tagging the protein! The problem is that most tags are too bulky, like trying to study a butterfly 🦋 with a bowling ball attached. To address this limitation, researchers at the Broad Institute developed two novel protein tags which were published…

Sumon Pratihar, Eric T. Kool and his team from Stanford University just published new paper in 𝘈𝘯𝘨𝘦𝘸𝘢𝘯𝘥𝘵𝘦 𝘊𝘩𝘦𝘮𝘪𝘦, unlocking a new way of selective RNA modification: “𝘚𝘦𝘲𝘶𝘦𝘯𝘤𝘦-𝘚𝘱𝘦𝘤𝘪𝘧𝘪𝘤 𝘐𝘯𝘴𝘵𝘢𝘭𝘭𝘢𝘵𝘪𝘰𝘯 𝘰𝘧 𝘈𝘳𝘺𝘭 𝘎𝘳𝘰𝘶𝘱𝘴 𝘪𝘯 𝘙𝘕𝘈 𝘷𝘪𝘢 𝘋𝘕𝘈-𝘊𝘢𝘵𝘢𝘭𝘺𝘴𝘵 𝘊𝘰𝘯𝘫𝘶𝘨𝘢𝘵𝘦𝘴” Key innovationDNA-directed approach that utilizes a DNA oligonucleotide carrying a nucleophilic amine to promote site-selective SNAr reaction at RNA…

E-STUB: A Precision Tool for Mapping E3 Ligase Substrates In march 2025, colleagues from Dana Faber and The Broad Institute published in 𝘕𝘢𝘵𝘶𝘳𝘦 𝘊𝘩𝘦𝘮𝘪𝘤𝘢𝘭 𝘉𝘪𝘰𝘭𝘰𝘨𝘺: “𝘜𝘣𝘪𝘲𝘶𝘪𝘵𝘪𝘯-𝘴𝘱𝘦𝘤𝘪𝘧𝘪𝘤 𝘱𝘳𝘰𝘹𝘪𝘮𝘪𝘵𝘺 𝘭𝘢𝘣𝘦𝘭𝘪𝘯𝘨 𝘧𝘰𝘳 𝘵𝘩𝘦 𝘪𝘥𝘦𝘯𝘵𝘪𝘧𝘪𝘤𝘢𝘵𝘪𝘰𝘯 𝘰𝘧 𝘌3 𝘭𝘪𝘨𝘢𝘴𝘦 𝘴𝘶𝘣𝘴𝘵𝘳𝘢𝘵𝘦𝘴” How it worksE-STUB (E3-Substrate Tagging by Ubiquitin Biotinylation) combines the principles of proximity labeling with the functional specificity of ubiquitin…

Top notch medchem building blocks got unlocked. Chemists from Enamine Ltd. published a robust route to saturated azabicyclic scaffolds (Angewandte Chemie): “𝘉𝘪𝘤𝘺𝘤𝘭𝘪𝘤 𝘐𝘴𝘰𝘴𝘵𝘦𝘳𝘦𝘴 𝘰𝘧 𝘗𝘺𝘳𝘪𝘥𝘪𝘯𝘦/𝘗𝘪𝘱𝘦𝘳𝘪𝘥𝘪𝘯𝘦: 𝘍𝘳𝘰𝘮 𝘚𝘺𝘯𝘵𝘩𝘦𝘴𝘪𝘴 𝘵𝘰 𝘈𝘱𝘱𝘭𝘪𝘤𝘢𝘵𝘪𝘰𝘯𝘴” Key innovationKOtBu/I₂/CO₂-mediated cyclization of cyclic alkenyl amines, delivering:✔️ 2-azabicyclo[2.2.2]octanes (35-73% yield)✔️ 2-azabicyclo[3.2.1]octane (69% yield)✔️ 2-azabicyclo[2.2.1]heptanes (75-85% yield)✔️ 7-azabicyclo[2.2.1]heptane (70% yield)✔️ 2-azabicyclo[3.1.1]heptanes (62-73% yield)✔️ 2-azabicyclo[2.1.1]hexanes (52-90% yield) ✅ 52–90% yield✅ Scales up to…

Why nucleoside analogs matter and why they’re hard to make Nucleoside analogs (NAs) are among the most successful drug classes in medicine, with more than 30 currently approved for treating viral infections such as HIV/AIDS and hepatitis, as well as certain cancers. These synthetic mimics of natural nucleosides act as antimetabolites through diverse mechanisms: inhibiting…

Direct monitoring of a binding interaction between biomolecules and their ligands is one of the cornerstones of early drug discovery, chemical biology and related disciplines. Assays that allow (semi)-quantitative measurements of the direct binding event, so-called target engagement (TE), became indispensable components of workflows for development or characterization of small molecules, peptides, antibodies, oligonucleotides and…

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❗✅…