Themed collection Celebrating International Women’s day 2026: Women in Chemical Biology

Chromodomains are epigenetic readers for histone methylation. Their selective targeting by small molecule or peptide inhibitors may serve as a novel way for disease intervention.

This review discusses the dichotomic role of reactive oxygen, nitrogen, and sulfur species (RONSS) in disease pathogenesis highlighting RONSS-targeted chemical probes and prodrugs for the detection and mitigation of RONSS-associated conditions.

A chemical reporter strategy is described for the metabolic labelling of ribitol-5-phosphate containing glycans, enabling bioorthogonal tagging of the glycoprotein α-dystroglycan.

A novel substrate was developed providing a high-throughput-compatible lanthanide luminescence assay that is selective for CDK5 over closely related CDK2.

The differential melting voltage (DMV) method evaluates and correlates the stability of individual protein glycoforms with molecular characteristics.

Cell-penetrating peptides enter cells through GAG-assisted translocation across the lipid bilayer.

Epigenetic sequencing methods largely rely on oxidation of 5mdC by Tet-enzymes. We report the development and characterization of novel Tet3-variants for oxidation-based bisulfite-free 5mdC-sequencing.

We combine E1/E2-mediated ubiquitin chain extension and sortase compatible ubiquitin to demonstrate a method for robust generation of discrete polyubiquitin chains and use sortase-mediated ligation to conjugate them to proteins site-specifically.

NARH activates SIRT5 through allosteric binding, enhancing desuccinylase activity on physiological substrates.

The red-shifted 5′-Me-D-LH₂ and 5′,7′-Me-D-LH₂, are promising substrates for future cell-based assays and in vivo imaging applications.

We developed a novel fluorescent indicator, TO-G-clamp, by conjugating a thiazole orange derivative with G-clamp, which identified unique RNA-binding small molecules missed by conventional indicators in fluorescent indicator displacement assay.

OGG1 lyase-activators are organocatalytic switches that enhance OGG1 initiated DNA repair by stimulating rudimentary activities through direct catalytic involvement, establishing de novo enzymatic functions on a widened substrate scope.

Identification of active site inhibitors of bacterial E3 ligases by covalent fragment screening coupled with high-throughput chemistry direct-to-biology (HTC-D2B).

Transcriptional regulatory proteins are frequent drivers of oncogenesis and common targets for drug discovery.

An affinity-based probe of the natural product nanchangmycin revealed a new mechanism by which this compound inhibits Zika virus infection.

2-Aminopurine fluorescence and simulations show that epigenetic modifications tune DNA structure and dynamics, with methylcytosine stabilizing stacking and hydroxymethylcytosine inducing flexible, less stacked conformations.

Bis-thiazole peptidomimetic TTh2 selectively binds and stabilizes the KRAS promoter G-quadruplex, leading to KRAS downregulation and inhibition of MAPK and Akt/mTOR pathways, demonstrating a novel strategy for targeting ''undruggable'' oncogenes.

In this paper, the structures of six different states (from pre-NAD⁺ binding to intermediate I) during the SIRT2 deacylase reaction and two catalytically essential mutants were captured to elucidate their functional roles in the enzymatic mechanism.

A common approach in living medicine engineering is modifying cell surfaces with nanomedicines. The choice of conjugation strategy and the chemical structure of the linker are crucial for living medicine design.

Galectin-4 differs from other galectins in carbohydrate-binding specificity, cellular and pathophysiological function, and roles in e.g. cancer progression, fibrosis, and ulcerative colitis, making potent, selective inhibitors desired.

The structurally diverse lipid A from the marine bacterium Rheinheimera japonica KMM 9513^T displays weak TLR4 agonism but strong antagonism against pro-inflammatory E. coli LPS, serving as a basis for developing novel immunomodulatory analogues.

Synthetic mucins with tunable glycosylation were prepared by a combination of NCA polymerization and enzymatic sialylation and fucosylation and were used to probe glycan-dependent effects on peptide structure and degradation.

The polyphosphate kinase 2 class III from an Erysipelotrichaceae bacterium is highly promiscuous. We determined the first crystal structure of the enzyme and applied structure-guided engineering to enable efficient access to ATP and GTP analogues.

Soluble peptidoglycan fragments produced by gut bacteria are key effectors in microbiota–host crosstalk.

The “turn-on” glucose transport-targeting molecular probe provides an effective tool for detection and evaluation of alterations in glucose uptake efficiency in cells and small organisms.

Peracetylated 4AzNeu5Ac is incorporated well into cell glycoconjugates. Deprotection via a thioglycoside facilitated chemoenzymatic synthesis of a C4-azido sialoside, which was studied for binding to Siglec-7 using native mass spectrometry.

The ancestry of animal kinases that regulate cellular responses to environmental stimuli, including stress, is understudied. A phenotypic screen uncovered a heat stress-activated protein kinase (SAPK) in the closest living relatives of animals.

Alanine-motif guided transactivation screening was implemented to detect bioactive microprotein sequences.

Macrocyclic peptide ligands developed via RaPID technology selectively bind and stabilize rhGBA1 in plasma at nanomolar concentrations without inhibiting endogenous GBA1, offering potential for combinatorial ERT-pharmacological chaperone for Gaucher disease.

We present iridium(III) probes for bioorthogonal metabolic labeling, enabling versatile bioimaging applications including super-resolution X-ray fluorescence nanoscopy and photoluminescence lifetime imaging microscopy to advance sialylation studies.

This study uncovers allosteric regulation in the reductase component (C1) of HPA 3-hydroxylase from Acinetobacter baumannii, where HPA binding enhances flavin production while reducing NADH consumption and H₂O₂ formation.

We developed a pull-down assay using His-Tag-containing PNAs equipped with a G-quadruplex (G4) ligand for selective recognition and quantification of a DNA target in a 96-well plate format, exploiting the DNAzyme properties of the G4–hemin complex.

Chemical inhibitor of cell wall alanylation sensitizes bacteria to diverse bacteriophages, revealing the widespread immunity conferred by cell wall modification.

A semi-rational and strategic-design approach using in silico tools and site-saturation mutagenesis with minimal experimental effort was used to engineer tryptophan 2-monooxygenase to obtain thermostable variants with the same enzyme activity.

N-7 is a novel pan-inhibitor targeting the m⁶A-RNA recognition by YTH domain readers.

We employ peptide-binding molecularly imprinted nanoparticles (MINPs) to probe the regulatory conformations and scaffolding interactions governing Pyk2 kinase activation.