Click Chemistry and Applications

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.

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.

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.

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.

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.

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.

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.

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.

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.

Photoclickable HaloTag Ligands for Spatiotemporal Multiplexed Protein Labeling on Living Cells

This paper develops a photoclickable labeling system for precise spatiotemporal protein labeling on living cells using visible light activation.

Mapping cellular targets of covalent cancer drugs in the entire mammalian body

This paper develops vCATCH to map covalent drug targets across the entire mouse body, revealing new tissue and cell type engagements for afatinib and ibrutinib.

Development of Second-Generation Acyl Silane Photoaffinity Probes for Cellular Chemoproteomic Profiling

This paper develops second-generation acyl silane photoaffinity probes for cellular chemoproteomic profiling, showing improved labeling properties compared to existing diazirine-based probes.

Discovery of RNA-Reactive Small Molecules Guides Design of Electrophilic Modules for RNA-Specific Covalent Binders

The paper identifies electrophilic compounds that covalently bind RNA and uses this insight to design an RNA-specific covalent binder for myotonic dystrophy type 1.

In vivo Antibody Painting for Next Generation Weight Loss Drugs

This paper develops an in vivo method to covalently link peptide drugs to native IgGs, demonstrating sustained weight loss and glucose management with GLP-1.

OpenEMMU: a versatile, open-source EdU multiplexing methodology for studying DNA replication and cell cycle dynamics

OpenEMMU improves EdU staining efficiency, brightness, and multiplexing for DNA replication and cell cycle analysis using affordable, open-source reagents.

Cell type-Specific In Vivo Proteomes with a Multi-copy Mutant Methionyl t-RNA Synthetase Mouse Line

This paper introduces a multicopy MetRS* mouse line to enhance cell type-specific in vivo protein labeling, enabling sensitive detection of newly synthesized proteins in sparse cell populations.

Chemical Proteomics Identifies Protein Ligands for Monoacylglycerol Lipids

The paper identifies protein ligands for monoacylglycerol lipids using chemical proteomics in mouse brain and cell lysates, revealing Hippocalcin as a novel ligand involved in calcium sensing.

Tuning Encodable Tetrazine Chemistry for Site-Specific Protein Bioorthogonal Ligations

This study develops a highly reactive and stable tetrazine amino acid for site-specific protein labeling, demonstrating improved encoding and ligation efficiency.

In-brain construction of receptor-based protease sensors by coupling ligand-directed chemistry and click chemistry

The paper develops a method to modify receptor proteins in the living mouse brain with fluorescent probes using ligand-directed and click chemistry, enabling high-resolution mapping of matrix metalloproteinase-9 activity near AMPARs.

Novel approaches to label the surface of S. aureus with DBCO for click chemistry-mediated deposition of sensitive cargo

This paper introduces two novel methods to incorporate DBCO into S. aureus peptidoglycan for SPAAC-mediated cargo labeling, showing improved stability and reduced toxicity compared to existing approaches.

A click chemistry-based biorthogonal approach for the detection and identification of protein lysine malonylation for osteoarthritis research

This study introduces MA-diyne, a click chemistry probe for detecting lysine malonylation in proteins, revealing its role in osteoarthritis by identifying targets and showing Sirtuin 5 regulation.

Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Iden-tify Covalent TLCD1 Inhibitors

The paper uses stereoprobes to identify covalent ligands for proteins, revealing TLCD1 as a lipid acyltransferase inhibited by OTP stereoprobes.

Bioorthogonal labeling of chitin in pathogenic Candida species reveals biochemical mechanisms of hyphal growth and homeostasis

The paper develops a chitin labeling method to study hyphal growth and homeostasis in Candida species, revealing mechanisms of morphological switching and potential antifungal targets.

Tools for intersectional optical and chemical tagging on cell surfaces

The paper introduces photo-click adapters for optical and chemical cell surface tagging, demonstrating applications in zebrafish embryo imaging and combinatorial cell labeling.

Genetic code expansion reveals site-specific lactylation in living cells reshapes protein function

This study uses genetic code expansion to site-specifically lactylate proteins in living cells, revealing lactylation's impact on enzyme activity and cellular function.