Themed collection Most popular 2025 chemical biology and medicinal chemistry articles

This Perspective reviews enzyme-activity imaging probes, centering on proteases and kinases, their architectures, and readout platforms. It underscores selectivity gains, theranostic designs, AI-assisted discovery, and growing clinical translation.

This Perspective assimilates developments in sulfonyl exchange chemical biology that have driven exciting advances in drug discovery and fundamental research over the last decade.

In the MAPK and PI3K pathways, upstream kinases Raf, MEK, and PI3K have one primary substrate, while downstream kinases ERK, AKT, and mTOR have multiple substrates. Mutations in PI3K/AKT/mTOR kinases are more abundant than mutations in MAPK kinases.

This review highlights the potential of multi-target-directed strategies that address amyloid-β aggregation, metal ion dyshomeostasis, and enzyme dysfunction, offering a comprehensive and effective approach to treating Alzheimer's disease.

Rational design yields topologically defined three-helix peptide assemblies and single-chain proteins. X-ray structures confirm atomic accuracy, with buried polar residues controlling structure and modulating stability.

This study aimed to elucidate the function of the bacterial bifunctional enzyme AsDMS, which catalyzes the conversion of farnesyl pyrophosphate into drimenol. Structural, mutational and biochemical analyses revealed the molecular mechanisms of AsDMS.

A data-driven multi-stage screening workflow was proposed to rapidly discover novel type I photosensitizers for RNA-targeted tumor photodynamic therapy.

ROS “bomb”: “D-12A” type single-molecule HPGQD synthesized via organic methods for PDT. It achieves a high ¹O₂ quantum yield (0.85), generating abundant ROS in 30 s and scavenging it after 10 min, thereby obviating prolonged patient photoprotection.

A “dual lock-and-key” nanophotosensitizer with ER-targeting capability was constructed for bioimaging-guided phototherapies, which can be activated only by weak acidity and GSH overexpression, leading to tumor specificity and biosafety.

We demonstrate that cluster-encoded but unrelated indole diterpene cyclases from different fungal classes catalyse a tetrahydropyran ring formation critical for efficient indole diterpene biosynthesis.

Accelerated production of insulin and glycosylated insulins by a rapid flow-based approach.

Using DNA-encoded libraries to identify protein binders is common, but finding molecules with functional activity remains challenging. We present here an encoded and pooled approach to discover catalysts for ubiquitin transfer.

The study explores the second branchpoint of the EFE catalytic mechanism, which determines the product distribution of ethylene and 3-hydroxypropionate formation using QM/MM simulations on WT and A198L variants of EFE.

Chiral histidine-rich peptides form coacervates that improve antigen delivery, T cell proliferation, and functional cytokine production.

An in situ activatable COF-based nanozyme is designed for targeted inhibition of the cGAS–STING pathway for AD treatment, which presents a promising strategy for AD treatment.

We discovered a fully synthetic non-degradative molecular glue for the ternary complex between FKBP12 and the FRB domain of mTOR by screening a library of FKBP12 ligands. Solving the ternary complex structure allowed significant potency enhancement.

BulbE TE, identified as a unique non-ribosomal peptide macrocyclizing thioesterase that catalyzes an N-acylindole linkage formation, offers valuable insight into the pivotal role of its catalytic residue in dictating nucleophile specificity.

Low steric hindrance, low error rate: conducting synthesis on a smooth surface made direct synthesis of 1000-nucleotide oligos a reality.

In celebration of our 15th anniversary and some of our most popular articles, Motomu Kanai reflects on the development of ketoABNO, following on from the report in 2012 in Chemical Science on catalysis mediated by ketoABNO (Chem. Sci., 2012, https://doi.org/10.1039/C2SC20699D).