Click Chemistry and Applications

Chemical proteomics suggests sofosbuvir is metabolically attached to proteins through a UMPylation-like pathway.

The paper identifies 120 proteins modified by sofosbuvir through a UMPylation-like pathway using chemical proteomics.

Determinants of cysteine coverage by chemoproteomics

This study identifies factors governing cysteine detection in chemoproteomics using machine learning and statistical filtering, showing that peptide properties and abundance are key determinants.

Rational Design of a Photoactivated Fluorescent Probe for Thiol-ene Mediated Protein Labelling

This paper introduces a photoactivated fluorescent probe, AbzSH, for selective alkene labelling in proteins and complex biological samples.

Ninhydrin as a covalent warhead for chemical proteomic-enabled discovery and selective engagement of reactive arginines

This paper introduces a ninhydrin-based warhead for selectively modifying arginine residues, enabling chemical proteomic studies and therapeutic targeting of reactive arginines.

Deep-learning-based design of an orthogonal self-labeling protein from K-Ras(G12C)

This paper designs an orthogonal self-labeling protein, LUCI-tag, using deep learning, which enables rapid and payload-agnostic labeling of proteins in live cells.

Natural product-derived azaphilones are selective scaffolds for covalent lysine liganding in live cells

This study identifies natural product-derived azaphilones as selective scaffolds for covalent lysine liganding in live cells, revealing bacterial chemotaxis as a major target pathway.

Molecular basis of AMPA receptor labeling by ligand-directed acyl imidazole chemistry in living neurons

This study uses QM calculations and MD simulations to elucidate the molecular mechanism of LDAI reagent labeling of AMPA receptors in living neurons, revealing how protein microenvironment influences reactivity.

A Metabolic Labeling Strategy for Tracking Protein Synthesis in Complex Biological Systems

This paper introduces TeACAT, a method to track newly synthesized proteins in mice by incorporating a non-canonical amino acid, enabling visualization and quantification with minimal perturbation.

CysLENS: Interpretable signatures of cysteine ligandability from enantiomeric chemoproteomics and protein language models

CysLENS identifies cysteine ligandability by integrating chemoproteomic data with protein language models to prioritize stereoselective interactions.

Small Molecule-Directed RNA Modification via Proximity-Driven Catalysis

This paper introduces a small molecule-directed method for site-selective RNA modification using DMAP catalysis and proximity-driven acylation, validated across multiple RNA types.

Chemoselective Bioconjugation Reveals Norepinephrinylation (NEylation) as a Widespread Post-Translational Modification in Cells

The paper develops a chemoselective bioconjugation method to detect and analyze NEylation, revealing it as a widespread PTM affecting protein function in cells.

Chemical Proteomic Profiling of the Histaminylation Proteome in Cancer Cells Unveils Uncharted Epigenetic Marks on Core Histones

This study identifies new TGM2-catalyzed histaminylation marks on core histones in cancer cells and reveals their crosstalk with γH2AX formation in DNA damage responses.

N-Terminal Alkylation of Proteins with Triazole-4-carbaldehyde for Targeted Liposome Engineering

This paper develops a method to attach proteins to liposomes via N-terminal alkylation using TA4C, enabling targeted delivery to EGFR-overexpressing cells.

Expanding the repertoire of chemically induced covalent neoantigens

This study develops a chemical proteomics platform to investigate covalent neoantigen formation and demonstrates immune cell recruitment through antibody-dependent cellular phagocytosis.

ESCAPE: assigning site-specific activity to covalent ligands in cells by prime editing

ESCAPE identifies covalent ligand-protein interactions by using prime editing to disrupt cysteine residues and assesses their impact on cellular phenotypes.

Phenotype-first covalent fragment screening identifies a synthetic lethal TYMS inhibitor in ATRX-deficient cells

The paper identifies a covalent fragment inhibitor of TYMS that selectively kills ATRX-deficient cells through replication stress.

A Chemoproteomic Atlas of the Human Purine Interactome for Regioselective Ligand Discovery

The paper develops a chemoproteomics platform to map the human purine interactome and identifies a regioselective ligand for ACAT2 with potential therapeutic applications in cancer.

Synthesis of Cyclopropene-Modified Fatty Acids Allows Single Cell Quantification of Uptake By Immune Cells

This study develops clickable fatty acids to quantify single-cell uptake by immune cells, finding polyunsaturated fatty acids are preferentially taken up by various immune cell types.

A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease ACTMAP

The paper compares acrylamide and butynamide stereoprobes to identify covalent inhibitors of the actin maturation protease ACTMAP in human cancer cells.

Rapid imaging of lysyl oxidase activity and fibrogenesis with a turn-on fluorophore

This paper introduces a fluorescent staining method to visualize LOX activity and fibrogenesis in tissue sections using a turn-on fluorophore, validated in mouse and human samples.

Click chemistry-based quantification of extracellular matrix turnover for drug screening and regenerative medicine

This paper introduces a click chemistry-based method to quantify ECM turnover, validated for drug screening and regenerative medicine applications.

ChemCell: Chemical Tethering of Large Biomolecules to Cell Surfaces through Diels-Alder Ligation

The paper introduces ChemCell, a method for attaching large biomolecules to cell surfaces using Diels-Alder ligation, enabling precise and efficient surface engineering.

Enhanced photo-crosslinking in living cells with high-intensity longwave ultraviolet light

This paper introduces a method using high-intensity longwave UV light to rapidly perform in-cell photo-crosslinking with minimal photodamage, enabling fast analysis of biomolecular interactions.

One-Pot Enzymatic ADDing of Click Chemistry Handles for Protein Immobilization and Bioconjugation of Small and Biomolecules

This paper introduces ADDing, an enzymatic method for attaching click chemistry handles to proteins using ApbE and a dedicated substrate, enabling efficient and versatile bioconjugation.

In Vivo Metabolic Tagging and Targeting of Circulating Red Blood Cells

This paper develops an in vivo method to label and target red blood cells with azido groups, enabling long-term cargo delivery and improved imaging.

A Modular Platform for Effector Discovery in Induced-Proximity Lysine Acetylation

This paper introduces a modular platform for rapidly evaluating PTM editing enzymes in living cells using induced proximity, demonstrating programmable acetylation of multiple substrates.

Cation-Cation Photosensitization for Protein Ligation and Intracellular Catalysis

This paper develops a photosensitized strategy for protein labelling using N-substituted pyridinium salts and a quinolinium scaffold, achieving efficient labelling in minutes with high selectivity for tryptophan residues.

Ultrafast tyrosine-based cell membrane modification via diazonium salts: a new frontier for biomedical applications

This paper introduces an ultrafast method for cell membrane modification using diazonium salts, enabling efficient and safe functionalization of various cell types for biomedical applications.

Mechanistically Defined Epoxide- and Aziridine-2-carboxamide Electrophiles Enable Stereoselective Covalent RNA Modulation

This paper introduces epoxide- and aziridine-2-carboxamide electrophiles that covalently target RNA with stereoselectivity, demonstrating their application to RNA targets like r(CUG)exp repeats and FMN riboswitches.

Cysteine reactive chloroalkane probe enables HaloTag ligation for downstream chemical proteomics analysis.

The paper introduces a cysteine-reactive chloroalkane probe for HaloTag ligation, enabling efficient and specific chemical proteomics analysis.