Click Chemistry and Applications

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.

INTERACT: Interactome Network Targeting via Enzyme Reactivity and Activity-based Chemoproteomic Tools

INTERACT identifies and quantifies active enzymes in host-pathogen interactions during infection without genetic manipulation.

Designer Aromatic Cations for Photo-Induced Protein Ligation, Imaging, and Intracellular Labelling at Extended Wavelengths

This paper designs aromatic cation salts that enable photo-induced protein labelling and imaging using longer wavelengths of light, achieving robust reactivity in live cells.

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.

Glycosylation-enabled Site-specific Growth Factor Engineering for Biomaterial Functionalization

This paper introduces a method to site-specifically modify growth factors with azido tags using glycosylation for biomaterial conjugation, demonstrating enhanced angiogenic responses in hydrogels.

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.

Thymidine kinase-independent click chemistry DNADetect™ probes as an EdU alternative for mammalian cell DNA labelling

The paper introduces DNADetect™ probes as an EdU alternative for DNA labeling in mammalian cells, bypassing thymidine kinase dependency and demonstrating efficient DNA incorporation.

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.

Regioselective Rapid Ene-type Reaction (RRER) Enables Bioconjugation of Histone Serotonylation

This study introduces a pH-controlled regioselective rapid ene-type reaction (RRER) for selectively modifying histone H3Q5 serotonylation and measuring its levels in cells and tissues.

Bioorthogonal cyclopropenones for investigating RNA structure

This paper develops bioorthogonal cyclopropenones to crosslink RNA and study its native structures in cells.

pH-Controlled chemoselective rapid azo-coupling reaction (CRACR) enables global profiling of serotonylation proteome in cancer cells

The paper develops a chemical proteomic method to globally profile serotonylation in cancer cells, identifying over 1,000 serotonylated proteins and their modification sites.

Detection of protein-protein interactions by bio-orthogonal fluorogenic proximity probes

This paper introduces fluorogenic probes to detect protein-protein interactions in both fixed and living cells, using dual-substrate recognition and antibody or genetic code expansion for detection.

CG-SLENP: A chemical genetics strategy to selectively label existing proteins and newly synthesized proteins

The paper introduces CG-SLENP, a chemical genetics method to selectively label existing and newly synthesized proteins, showing differential modulation of these pools by a small molecule ligand.

DrugMap: A quantitative pan-cancer analysis of cysteine ligandability

DrugMap quantitatively analyzes cysteine ligandability across 416 cancer cell lines, revealing redox state, conformational changes, and mutations as drivers of variability, and identifies covalent inhibitors targeting NFκB1 and SOX10.

Bioorthogonal labeling enables in situ fluorescence imaging of expressed gas vesicle nanostructures

This paper introduces a bioorthogonal labeling method to fluorescently visualize gas vesicles in cells, enabling analysis of their size and distribution.

Trifunctional fatty acid derivatives demonstrate the impact of diazirine placement

The paper synthesizes three palmitic acid derivatives with diazirine at different positions and shows that end-position diazirines crosslink distinct protein subsets.

Assigning functionality to cysteines by base editing of cancer dependency genes

The paper uses base editing to assess the functional impact of cysteine mutations in cancer dependency genes, identifying essential and ligandable cysteines for drug development.

Direct fluorescent labeling of NF186 and NaV1.6 in living primary neurons using bioorthogonal click chemistry

This paper develops a method to label and image AIS proteins in living neurons using unnatural amino acids and bioorthogonal click chemistry, demonstrating its application to study NaV1.6 variants.