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Luminescent and cell-permeable macrocyclic terbium complexes called CoraFluors enable the detection of ligand–target engagement in cells by time-resolved FRET. The image shows a protein target (in purple) lit up by CoraFluors.
Ferroptosis is a regulated form of non-apoptotic cell death implicated in pathological settings. To be exploited clinically, ferroptosis requires reagents that unequivocally detect ferroptosis in human and animal tissues. Such tools may enable development of ferroptosis-based medicines for diverse diseases.
Graspetides are an important class of ribosomal natural products with potent bioactivities. New structural information provides insights into substrate recognition and catalysis, including a rare glimpse into the interactions between a tailoring enzyme and the core of the precursor peptide.
RNA modifications are emerging regulators of development and disease. A metabolic labeling approach using 5-fluorocytidine (5-FCyd) allows the mechanism-based profiling of several RNA-modifying enzymes and potentially links their activity to novel RNA targets.
Structural and biochemical analysis of the plesiocin macrocyclase enzyme PsnB revealed that, unlike other ribosomal natural products, the core region of the precursor peptide enhances its interaction with the enzyme via conserved glutamate residues.
The development of a photocage-nanobody based technology enabled in-depth analysis of live cells from tissues while retaining their spatial information.
Partial antagonists of the ER transmembrane kinase/endoribonuclease IRE1ɑ were identified that preserve splicing of downstream RNA substrates such as XBP1, enabling cellular survival.
Trivalent PROTACs are reported as a strategy to increase protein degradation efficacy and therapeutic window by combining avidity of target engagement with cooperativity to form highly favorable and productive ternary complexes.
CoraFluors, a class of macrocyclic terbium complexes for use in time-resolved FRET, exhibit physicochemical properties desirable for biological studies, including characterization of Keap1 ligands and HDAC1 target engagement profiling in live cells.
A chemoproteomic strategy called RNA-mediated activity-based protein profiling (RNABPP) was developed to profile RNA-modifying enzymes in live cells and uncover the RNA substrates of the human dihydrouridine synthase DUS3L.
Using short-read sequencing data, Evoracle reconstructs full-length genotypes and fitness during directed evolution experiments, and can identify low-frequency variants before they can be identified using consensus mutations.
Surface protein tagging and mass spectrometry-based proteomics applied in a rabbit cholera model system identifies proteins involved in Vibrio cholera-host cell interactions and defines a cholera toxin-dependent role for host surfactant protein D.