For decades, ubiquitin has been considered almost exclusively as a protein tag. Its C-terminal Gly-Gly motif forms isopeptide (or occasionally thio-/oxy-ester) bonds with Lys, Cys, Ser or Thr residues, marking proteins for degradation, trafficking or regulation. While a handful of reports have suggested that ubiquitin can also be attached to sugars, lipids, nucleic acids or…
While transition metals drive powerful bond-forming reactions in synthetic chemistry, their use for covalent modification of biomolecules has been largely underexplored and restricted to isolated proteins in vitro. Aryl-metal reagents for protein S-arylation have so far been dominated by palladium and gold complexes, but these systems require sterically bulky phosphine ligands that promote reductive elimination,…
About 85% of disease-related proteins lack suitable binding pockets for conventional drug discovery. While RNA-targeting approaches like siRNAs have shown promise (with several FDA approvals), they struggle with poor cellular uptake, limited tissue specificity, and complex, costly synthesis. Researchers from Peking University Shenzhen Graduate School introduce a novel modality for targeting “undruggable” proteins through RNA…
How can bioorthogonal chemistry and mitochondrial targeting rewrite cancer immunotherapy? By creating enzyme-responsive nanoparticles that self-assemble in tumors and chemically “click” with an arsenic payload, scientists achieved complete tumor eradication and durable immune memory. Two main components – two small molecules (Fig. panel b)๐ ๐๐ซ๐จ๐๐ ๐-๐๐๐-๐๐๐:An ALP-responsive small molecule comprising a phosphate-caged fluorophore (mCy), a…
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 ๐ฆ 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 ๐๐ฏ๐จ๐ฆ๐ธ๐ข๐ฏ๐ฅ๐ต๐ฆ ๐๐ฉ๐ฆ๐ฎ๐ช๐ฆ, unlocking a new way of selective RNA modification: “๐๐ฆ๐ฒ๐ถ๐ฆ๐ฏ๐ค๐ฆ-๐๐ฑ๐ฆ๐ค๐ช๐ง๐ช๐ค ๐๐ฏ๐ด๐ต๐ข๐ญ๐ญ๐ข๐ต๐ช๐ฐ๐ฏ ๐ฐ๐ง ๐๐ณ๐บ๐ญ ๐๐ณ๐ฐ๐ถ๐ฑ๐ด ๐ช๐ฏ ๐๐๐ ๐ท๐ช๐ข ๐๐๐-๐๐ข๐ต๐ข๐ญ๐บ๐ด๐ต ๐๐ฐ๐ฏ๐ซ๐ถ๐จ๐ข๐ต๐ฆ๐ด” 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 ๐๐ข๐ต๐ถ๐ณ๐ฆ ๐๐ฉ๐ฆ๐ฎ๐ช๐ค๐ข๐ญ ๐๐ช๐ฐ๐ญ๐ฐ๐จ๐บ: “๐๐ฃ๐ช๐ฒ๐ถ๐ช๐ต๐ช๐ฏ-๐ด๐ฑ๐ฆ๐ค๐ช๐ง๐ช๐ค ๐ฑ๐ณ๐ฐ๐น๐ช๐ฎ๐ช๐ต๐บ ๐ญ๐ข๐ฃ๐ฆ๐ญ๐ช๐ฏ๐จ ๐ง๐ฐ๐ณ ๐ต๐ฉ๐ฆ ๐ช๐ฅ๐ฆ๐ฏ๐ต๐ช๐ง๐ช๐ค๐ข๐ต๐ช๐ฐ๐ฏ ๐ฐ๐ง ๐3 ๐ญ๐ช๐จ๐ข๐ด๐ฆ ๐ด๐ถ๐ฃ๐ด๐ต๐ณ๐ข๐ต๐ฆ๐ด” How it worksE-STUB (E3-Substrate Tagging by Ubiquitin Biotinylation) combines the principles of proximity labeling with the functional specificity of ubiquitin…
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…
For decades, creating proteins with extended backbones (ฮฒ, ฮณ, ฮด-amino acids) inside living cells has been challenging. Researchers at University of California, Berkeley (Alanna Schepartz, Leah Roe), Yale University, Amgen and collaborators developedย BEAR reactionsย to address this challenge. ๐๐ก๐ฒ ๐๐จ๐๐ฌ ๐ญ๐ก๐ข๐ฌ ๐ฆ๐๐ญ๐ญ๐๐ซ?โ Extension of backbone can lead to improved phys-chem propertiesโ Better stability and resistance to…
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:๐ธ The SAM analogues are chemically reactive (labile aziridine rings…