A Protein Cleavage Platform Based on Selective Formylation at Cysteine Residues.

Site-selective cleavage of the peptide backbone in proteins is an important class of post-translational modification (PTM) in nature. However, the organic chemistry for such site-selective peptide bond cleavages has yet to be fully explored. Herein, we report cysteine -formylation as a means of selective protein backbone cleavage.

Targeted Covalent Modification Strategies for Drugging the Undruggable Targets.

The term "undruggable" refers to proteins or other biological targets that have been historically challenging to target with conventional drugs or therapeutic strategies because of their structural, functional, or dynamic properties. Drugging such undruggable targets is essential to develop new therapies for diseases where current treatment options are limited or nonexistent. Thus, investigating methods to achieve such drugging is an important challenge in medicinal chemistry.

Conversion of silent synapses to AMPA receptor-mediated functional synapses in human cortical organoids.

Despite the crucial role of synaptic connections and neural activity in the development and organization of cortical circuits, the mechanisms underlying the formation of functional synaptic connections in the developing human cerebral cortex remain unclear. We investigated the development of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission using human cortical organoids (hCOs) derived from induced pluripotent stem cells. Two-photon Ca⁺ imaging revealed an increase in the frequency and amplitude of spontaneous activity in hCOs on day 80 compared to day 50.

Selective Labeling of Phosphatidylcholine to Track Their Translocation Between Organelles in Living Cells.

Phosphatidylcholine (PC) is a major phospholipid that forms biological membranes in eukaryotes. PC is mainly synthesized in the endoplasmic reticulum (ER) and Golgi apparatus and then transported to other organelle membranes via multiple mechanisms. Such interorganelle lipid transport is thought to play an important role in the maintenance of cell morphology, organelle functions, and homeostasis, though the details of this process have not yet been well investigated.