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Abstract A practical method is introduced for the catalytic conversion of terminal alkynes into α-substituted vinyl boronic esters. The process employs catalytic amounts of nanoparticle-supported gold catalysts and catalytic amounts of copper to effect the overall transformation. 

Thiophene-containing heteroarenes are one of the most well-known classes of π-conjugated building blocks for photoactive molecules. Isomeric naphthodithiophenes (NDTs) are at the forefront of this research area due to their straightforward synthesis and derivatization. Notably, NDT geometries that are bent – such as naphtho[2,1-b:3,4-b']dithiophene (a-NDT) and naphtho[1,2-b:4,3-b']dithiophene (b-NDT) – are seldom employed as photoactive small molecules. This report investigates how remote substituents impact the photophysical properties of isomeric a- and b-NDTs. The orientation of the thiophene units plays a critical role in the emission: in the a(OHex)R2 series conjugation from the end- caps to the NDT core is apparent, while in the b(Oi-Pent)R2 series minimal change is observed unless strong electron acceptors, such as b(Oi-Pent)(PhCF3)2, are employed. This push–pull acceptor–donor– acceptor (A–D–A) fluorophore exhibits positive fluorosolvatochromism that correlates with increasing solvent polarity parameter, ET(30). In total, these results highlight how remote substituents are able to modulate the emission of isomeric bent NDTs. 

The combination of ultra-long (UL) Oxford Nanopore Technologies (ONT) sequencing reads with long, accurate Pacific Bioscience (PacBio) High Fidelity (HiFi) reads has enabled the completion of a human genome and spurred similar efforts to complete the genomes of many other species. However, this approach for complete, “telomere-to-telomere” genome assembly relies on multiple sequencing platforms, limiting its accessibility. ONT “Duplex” sequencing reads, where both strands of the DNA are read to improve quality, promise high per-base accuracy. To evaluate this new data type, we generated ONT Duplex data for three widely studied genomes: human HG002, Solanum lycopersicum Heinz 1706 (tomato), and Zea mays B73 (maize). For the diploid, heterozygous HG002 genome, we also used “Pore-C” chromatin contact mapping to completely phase the haplotypes. We found the accuracy of Duplex data to be similar to HiFi sequencing, but with read lengths tens of kilobases longer, and the Pore-C data to be compatible with existing diploid assembly algorithms. This combination of read length and accuracy enables the construction of a high-quality initial assembly, which can then be further resolved using the UL reads, and finally phased into chromosome-scale haplotypes with Pore-C. The resulting assemblies have a base accuracy exceeding 99.999% (Q50) and near-perfect continuity, with most chromosomes assembled as single contigs. We conclude that ONT sequencing is a viable alternative to HiFi sequencing for de novo genome assembly, and provides a multirun single-instrument solution for the reconstruction of complete genomes. 

Abstract Protein serine/threonine/tyrosine (S/T/Y) phosphorylation is an essential and frequent post-translational modification in eukaryotes, but historically has been considered less prevalent in bacteria because fewer proteins were found to be phosphorylated and most proteins were modified to a lower degree. Recent proteomics studies greatly expanded the phosphoproteome of Escherichia coli to more than 2000 phosphorylation sites (phosphosites), yet mechanisms of action were proposed for only six phosphosites and fitness effects were described for 38 phosphosites upon perturbation. By systematically characterizing functional relevance of S/T/Y phosphorylation in E. coli metabolism, we found 44 of the 52 mutated phosphosites to be functional based on growth phenotypes and intracellular metabolome profiles. By effectively doubling the number of known functional phosphosites, we provide evidence that protein phosphorylation is a major regulation process in bacterial metabolism. Combining in vitro and in vivo experiments, we demonstrate how single phosphosites modulate enzymatic activity and regulate metabolic fluxes in glycolysis, methylglyoxal bypass, acetate metabolism and the split between pentose phosphate and Entner-Doudoroff pathways through mechanisms that include shielding the substrate binding site, limiting structural dynamics, and disrupting interactions relevant for activity in vivo. 

Abstract Despite the critical role played by carbon monoxide (CO) in physiological and pathological signaling events, current approaches to deliver this messenger molecule are often accompanied by off‐target effects and offer limited control over release kinetics. To address these challenges, we develop an electrochemical approach that affords on‐demand release of CO through reduction of carbon dioxide (CO₂) dissolved in the extracellular space. Electrocatalytic generation of CO by cobalt phthalocyanine molecular catalysts modulates signaling pathways mediated by a CO receptor soluble guanylyl cyclase. Furthermore, by tuning the applied voltage during electrocatalysis, we explore the effect of the CO release kinetics on CO‐dependent neuronal signaling. Finally, we integrate components of our electrochemical platform into microscale fibers to produce CO in a spatially‐restricted manner and to activate signaling cascades in the targeted cells. By offering on‐demand local synthesis of CO, our approach may facilitate the studies of physiological processes affected by this gaseous molecular messenger.