Themed collection Small molecules for chemical biology

Chemical modulation of the RNA m⁶A demethylase FTO for cancer therapy.

Overview of the Wnt signaling pathway and targets of Wnt activators.

The structures, biosynthesis, and modes of action of albomycin, microcin C and agrocin 84, antibiotics targeting aminoacyl-tRNA synthetases, are reviewed. Using bioinformatics several new putative aminoacyl-tRNA synthetase inhibitors are predicted.

Supramolecular assemblies of small molecules, exhibiting emergent properties, are becoming a new and dynamic molecular platform for biological functions and for developing novel therapeutic approaches.

This review discusses the development of sulfonyl–triazoles and highlights the merits and opportunities for deploying this sulfur electrophile for biological discovery.

Modified nucleoside triphosphates (NTPs) are invaluable tools to probe bacterial enzymatic mechanisms, develop novel genetic material, and engineer drugs and proteins with new functionalities.

CDy1 is a powerful tool to distingusih embryonic stem cells for reprogramming studies and regeneration medicine.

A dual-resin system was developed that united confocal-fluorescent imaging for hit identification and microscale NMR for hit isolation and structure elucidation. Using this approach, we identified two natural products that bound to the inhibitor of apoptosis protein, survivin.

We report the rational design, novel syntheses and biophysical and in silico evaluation of tryptophan-inspired tool compounds to probe the illusive MOA of the clinically-relevant heme-dioxygenase protein, IDO1.

Alkyl chain extension and aryl methylation can be employed to enhance mitochondrial uptake in triphenylphosphonium vectors. Here we compare these complementary strategies and their mitochondrial-targeting effects using a modular synthetic approach.

Human semen contains various amyloidogenic peptides derived from Prostatic Acid Phosphatase (PAP) and Semenogelin proteins that are capable of enhancing HIV-1 infection when assembled into fibrils.

Phosphinate electrophiles are developed as activity-based probes for serine proteases. They can be used for gel-based profiling as well as for microscopy-based detection, and their use is here demonstrated on neutrophil serine proteases.

Diazirine-containing photoaffinity probes, based on the potent and selective TRPC1/4/5 channel inhibitor Pico145, allowed the development of an assay to probe cellular interactions between TRPC5 protein and xanthine-based TRPC5 channel modulators.

We identified potent, functionalisable BMX inhibitors and revealed their covalent mode of binding to BMX by X-ray crystallography.

Discovery of a potent, small-molecule, fluorescent agonist of the follicle-stimulating hormone receptor (FSHR) for selective staining of FSHR-expressing cells.

Discovery and optimization of de novo macrocyclic peptide binders of Wnt3a through RaPID screening against an afamin-stabilized Wnt3a complex, capable of inhibiting Wnt signalling by direct interaction to the Wnt protein.

UDP-N-acetylglucosamine pyrophosphorylase (UAP1) catalyses the last step in eukaryotic biosynthesis of uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc), converting UTP and GlcNAc-1P to the sugar nucleotide.