DeKinomics pulse-chases kinase functions in living cells.

Cellular context is crucial for understanding the complex and dynamic kinase functions in health and disease. Systematic dissection of kinase-mediated cellular processes requires rapid and precise stimulation ('pulse') of a kinase of interest, as well as global and in-depth characterization ('chase') of the perturbed proteome under living conditions. Here we developed an optogenetic 'pulse-chase' strategy, termed decaging kinase coupled proteomics (DeKinomics), for proteome-wide profiling of kinase-driven phosphorylation at second-timescale in living cells.

Bioorthogonal Photocatalytic Decaging-Enabled Mitochondrial Proteomics.

Spatiotemporally resolved dissection of subcellular proteome is crucial to our understanding of cellular functions in health and disease. We herein report a bioorthogonal and photocatalytic decaging-enabled proximity labeling strategy (CAT-Prox) for spatiotemporally resolved mitochondrial proteome profiling in living cells. Our systematic survey of the photocatalysts has led to the identification of Ir(ppy)bpy as a bioorthogonal and mitochondria-targeting catalyst that allowed photocontrolled, rapid rescue of azidobenzyl-caged quinone methide as a highly reactive Michael acceptor for proximity-based protein labeling in mitochondria of live cells.

Spatiotemporally resolved subcellular phosphoproteomics.

Proteome-wide profiling of protein phosphorylation has been widely used to reveal the underlying mechanism of diverse cellular signaling events. Yet, characterizing subcellular phosphoproteome with high spatial-temporal resolution has remained challenging. Herein, we developed a subcellular-specific uncaging-assisted biotinylation and mapping of phosphoproteome (SubMAPP) strategy to monitor the phosphorylation dynamics of subcellular proteome in living cells and animals.

MYORG Mutation Heterozygosity Is Associated With Brain Calcification.

Background: Biallelic mutations in the MYORG gene were first identified as the cause of recessively inherited primary familial brain calcification. Interestingly, some heterozygous carriers also exhibited brain calcifications.

Objectives: To further investigate the role of single heterozygous MYORG mutations in the development of brain calcifications.

Computational and experimental investigation on the BCl promoted intramolecular amination of alkenes and alkynes.

The BX3 promoted transition-metal-free borylative cyclizations have recently attracted increasing attention. In 2015, the Li group reported a BCl3 mediated aminoboration of unfunctionalized olefins. In their originally proposed reaction pathways, the overall reaction barrier was calculated to be about 35 kcal mol-1, which is too high to be reasonable for a reaction that smoothly occurs at room temperature.

Bioorthogonal release of sulfonamides and mutually orthogonal liberation of two drugs.

Sulfonamide derivatives have been used in pharmaceutics for decades. Here we report a new approach to release sulfonamides efficiently using a bioorthogonal reaction of sulfonyl sydnonimines and dibenzoazacyclooctyne (DIBAC). The second-order rate constant of the cycloaddition reaction can be up to 0.

Origins of halogen effects in bioorthogonal sydnone cycloadditions.

Halogen substituents increase sydnone cycloaddition reactivities substantially. Fluoro-sydnones are superior to bromo- and chloro-sydnones, and can achieve extremely high second-order rate constants with strained alkynes. Computational studies have revealed the fluorine substituent increases the reactivity of sydnone mainly by lowering its distortion energy.