Articles in 2023

DNA-encoded libraries are a powerful tool to identify novel chemical inducers of proximity such as targeted protein degraders, even without a known binder for the target protein.

Development of live-cell target engagement approaches to query MEK-bound binary and ternary complexes reveals the distinct pharmacology of clinical MEK inhibitors at specific assemblies composed of MEK, RAF, KSR and 14-3-3.

Lis1 binding to the AAA+ ring of dynein increases the microtubule affinity and slows dynein motility. Lis1 binding to the stalk of dynein restricts the sliding of the coiled coils and slows detachment from microtubules under load.

A high-throughput DNA-encoded library (DEL)-based screening approach was developed for the discovery of proximity-inducing small molecules.

Chemical proteomics profiling of 1,183 kinase inhibitors from past drug discovery projects revealed a large number of reasonably selective compounds for several kinases such as SYK and CK2.

Defining subcellular locations and interacting partners for proteins accelerates their functional characterization. A new in vivo tagging approach achieves both for mitochondrial matrix proteins and helps connect a key oxidoreductase to coenzyme Q biosynthesis.

Genetically encoded tools to manipulate redox metabolism are in high demand for investigating the underlying mechanism of cofactor imbalances in mammalian systems. A new tool enables the induction and interrogation of NADH reductive stress.

The development of a transgenic mouse line that expresses mitochondrial matrix-targeted APEX2 combined with proteome analysis identified RTN4IP1, which serves as an NAD(P)H oxidoreductase required for respiration and CoQ biosynthesis.

NOXs are vital ROS-producing enzymes with roles in cell function and cancer. Here the authors combine computational and experimental methods to validate inhibitors for human NOX enzymes, opening avenues for redox biology-related cancer drug development.

A soluble bacterial transhydrogenase from Escherichia coli (EcSTH) was validated as a genetically encoded tool to induce NADH reductive stress in mammalian cells revealing unique transcriptional and metabolic signatures.

Traditional production of therapeutic secretory proteins often experiences delays between protein synthesis and therapeutic effects. An inducible protease-dependent protein secretion technique allows the immediate secretion of pre-translated biotherapeutic agents after exposure to chemical cues, tumor-specific antigens or photons.

Park et al. redesigned the abscisic acid-induced dimerization module to respond to diverse ligands and function orthogonally to the natural modules, enabling synthetic biological circuit design in plants and yeast.

A controllable protease-based protein secretion platform was developed for the rapid delivery of user-defined therapeutic protein secretion in response to FDA-approved drugs, tumor antigen and light, enabling cell-based precision therapies.

We developed a versatile lipid probe — MAO–SiR — to visualize the structure and dynamics of the inner mitochondrial membrane (IMM). MAO–SiR assembles in situ from two cell-permeant small molecules to image the IMM selectively, continuously and at super resolution for extended periods of time without extensive photobleaching or toxicity.

A lipid-like small molecule, MAO-N₃, was developed to assemble inner mitochondrial membrane-specific probes for confocal and various super-resolution microscopy techniques, with significantly improved time-lapse capability and minimal toxicity.