Fuel‐driven self‐assemblies are gaining ground for creating autonomous systems and materials, whose temporal behavior is preprogrammed by a reaction network. However, up to now there has been a lack of simple external control mechanisms of the transient behavior, at best using remote and benign light control. Even more challenging is to use different wavelengths to modulate the reactivity of different components of the system, for example, as fuel or building blocks. Success would enable such systems to navigate along different trajectories in a wavelength‐dependent fashion. Herein, we introduce the first examples of light control in ATP‐fueled, dynamic covalent DNA polymerization systems organized in an enzymatic reaction network of concurrent ATP‐powered ligation and restriction. We demonstrate concepts for light activation and modulation by introducing caged ATP derivatives and caged DNA building blocks, making it possible to realize light‐activated fueling, self‐sorting in structure and behavior, and transition across different wavelength‐dependent dynamic steady states.

β-Cells respond directly to the intracellular photochemical release of caged inositol pyrophosphate isomers with modulations of oscillations in cytosolic Ca2+.

Enzymatic hydroxylation of unactivated primary carbons is generally associated with the use of molecular oxygen as co-substrate for monooxygenases. However, in anaerobic cholesterol-degrading bacteria such as Sterolibacterium denitrificans the primary carbon of the isoprenoid side chain is oxidised to a carboxylate in the absence of oxygen. Here, we identify an enzymatic reaction sequence comprising two molybdenum-dependent hydroxylases and one ATP-dependent dehydratase that accomplish the hydroxylation of unactivated primary C26 methyl group of cholesterol with water: (i) hydroxylation of C25 to a tertiary alcohol, (ii) ATP-dependent dehydration to an alkene via a phosphorylated intermediate, (iii) hydroxylation of C26 to an allylic alcohol that is subsequently oxidised to the carboxylate. The three-step enzymatic reaction cascade divides the high activation energy barrier of primary C-H bond cleavage into three biologically feasible steps. This finding expands our knowledge of biological C-H activations beyond canonical oxygenase-dependent reactions.

There has been a recent upsurge in the study and application of approaches utilizing cyclotriphosphate 1 (cyclo‐TP, also known as trimetaphosphate, TMP) and/or proceeding through its analogues in synthetic chemistry to access modified oligo‐ and polyphosphates. This is especially useful in the area of chemical nucleotide synthesis, but by no means restricted to it. Enabled by new high yielding and easy‐to‐implement methodologies, these approaches promise to open up an area of research that has previously been underappreciated. Additionally, refinements of concepts of prebiotic phosphorylation chemistry have been disclosed that ultimately rely on cyclo‐TP 1 as a precursor, placing it as a potentially central compound in the emergence of life. Given the importance of such concepts for our understanding of prebiotic chemistry in combination with the need to readily access modified polyphosphates for structural and biological studies, this paper will discuss selected recent developments in the field of cyclo‐TP chemistry, briefly touch on ultraphosphate chemistry, and highlight areas in which further developments can be expected.

Inositol pyrophosphates constitute a family of hyperphosphorylated signaling molecules involved in the regulation of glucose uptake and insulin sensitivity. While our understanding of the biological roles of inositol heptaphosphates (PP-InsP 5 ) has greatly improved, the functions of the inositol octaphosphates ((PP) 2 -InsP 4 ) have remained unclear. Here we present the synthesis of two enantiomeric cell-permeant and photocaged (PP) 2 -InsP 4 derivatives and apply them to study the functions in living β-cells. Photorelease of the naturally occurring isomer 1,5-(PP) 2 -InsP 4 led to an immediate and concentration-dependent reduction of intracellular calcium oscillations, while other caged inositol pyrophosphates (3,5-(PP) 2 -InsP 4 , 5-PP-InsP 5 , 1-PP-InsP 5 , 3-PP-InsP 5 ) showed no immediate effect. Furthermore, uncaging of 1,5-(PP) 2 -InsP 4 but not 3,5-(PP) 2 -InsP 4 induced translocation of the C2AB domain of granuphilin from the plasma membrane to the cytosol. Granuphilin is involved in membrane docking of secretory vesicles. This suggests that 1,5-(PP) 2 -InsP 4 impacts β-cell activity by regulating granule localization and/or priming and calcium signaling in concert.

Harmful algal blooms are becoming more prevalent all over the world, and identification and mechanism of action studies of the responsible toxins serve to protect ecosystems, livestock and humans alike. In this study, the chlorosulfopeptide aeruginosin 828A, which rivals in crustacean toxicity the well-known toxin microcystin LR, has been synthesized for the first time. In addition, three congeners with different permutations of the chloride and sulfate groups have been prepared, thereby allowing for toxicity studies without the risk of contamination by other natural toxins. Toxicity assays with the sensitive crustacean Thamnocephalus platyurus demonstrated that the introduction of a sulfate group leads to pronounced toxicity, while NMR spectroscopic evidence suggests that the chloride substituent modulates the conformation, which influences protease inhibitory activity.

Fuel‐driven self‐assemblies are gaining ground for creating autonomous systems and materials, whose temporal behavior is preprogrammed by a reaction network. However, up to now there has been a lack of simple external control mechanisms of the transient behavior, at best using remote and benign light control. Even more challenging is to use different wavelengths to modulate the reactivity of different components of the system, for example, as fuel or building blocks. Success would enable such systems to navigate along different trajectories in a wavelength‐dependent fashion. Herein, we introduce the first examples of light control in ATP‐fueled, dynamic covalent DNA polymerization systems organized in an enzymatic reaction network of concurrent ATP‐powered ligation and restriction. We demonstrate concepts for light activation and modulation by introducing caged ATP derivatives and caged DNA building blocks, making it possible to realize light‐activated fueling, self‐sorting in structure and behavior, and transition across different wavelength‐dependent dynamic steady states.

Photocages have been successfully applied in cellular signaling studies for the controlled release of metabolites with high spatio-temporal resolution. Commonly, coumarin photocages are activated by UV light and the quantum yields of uncaging are relatively low, which can limit their applications in vivo. Here, syntheses, the determination of the photophysical properties, and quantum chemical calculations of 7-diethylamino-4-hydroxymethyl-thiocoumarin (thio-DEACM) and caged adenine nucleotides are reported and compared to the widely used 7-diethylamino-4-hydroxymethyl-coumarin (DEACM) caging group. In this comparison, thio-DEACM stands out as a phosphate cage with improved photophysical properties, such as red-shifted absorption and significantly faster photolysis kinetics.