67583-85-1Relevant articles and documents
Dynamic Exchange of Substituents in a Prebiotic Organocatalyst: Initial Steps towards an Evolutionary System
Bechtel, Maximilian,Closs, Anna C.,Trapp, Oliver
supporting information, (2021/12/01)
All evolutionary biological processes lead to a change in heritable traits over successive generations. The responsible genetic information encoded in DNA is altered, selected, and inherited by mutation of the base sequence. While this is well known at the biological level, an evolutionary change at the molecular level of small organic molecules is unknown but represents an important prerequisite for the emergence of life. Here, we present a class of prebiotic imidazolidine-4-thione organocatalysts able to dynamically change their constitution and potentially capable to form an evolutionary system. These catalysts functionalize their building blocks and dynamically adapt to their (self-modified) environment by mutation of their own structure. Depending on the surrounding conditions, they show pronounced and opposing selectivity in their formation. Remarkably, the preferentially formed species can be associated with different catalytic properties, which enable multiple pathways for the transition from abiotic matter to functional biomolecules.
Mouse long-chain acyl-CoA synthetase 1 is active as a monomer
Dykstra, Holly,Fisk, Chelsea,LaRose, Cassi,Waldhart, Althea,Meng, Xing,Zhao, Gongpu,Wu, Ning
, (2021/02/01)
Fatty acids are essential cellular building blocks and a major energy source. Regardless of their metabolic fate, fatty acids first need to be activated by forming a thioester with a coenzyme A group. This reaction is carried out by acyl-CoA synthetases (ACSs), of which ACSL1 (long-chain acyl-CoA synthetase 1) is an important member. Two bacterial homologues of ACSL1 crystal structures have been solved previously. One is a soluble dimeric protein, and the other is a monomeric peripheral membrane protein. The mammalian ACSL1 is a membrane protein with an N-terminal transmembrane helix. To characterize the mammalian ACSL1, we purified the full-length mouse ACSL1 and reconstituted it into lipid nanodiscs. Using enzymatic assays, mutational analysis, and cryo-electron microscopy, we show that mouse ACSL1 is active as a monomer.
Synthesis method and application of vidarabine monophosphate
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Paragraph 0074; 0084-0086, (2021/07/28)
The invention belongs to the field of medicine synthesis, and discloses a synthesis method and application of vidarabine monophosphate. According to the synthesis method, 5-iodo-2-((phosphonooxy) methyl)-4-(tosyloxy)tetrahydrofuran-3-yl acetate and tert-butyl (8-hydroxy-9H-purin-6-yl)carbamate are subjected to condensation, epoxidation, ring opening and desulfurization reaction, and the vidarabine monophosphate is synthesized. According to the synthesis method of vidarabine monophosphate, provided by the invention, the industrial production steps are further simplified, the total reaction yield is improved, and the industrial production cost is reduced. The method is suitable for synthesizing vidarabine monophosphate, and the synthesized vidarabine monophosphate is used for preparing vidarabine monophosphate for injection.
Reduced nicotinamide mononucleotide is a new and potent nad+ precursor in mammalian cells and mice
Zapata-Pérez, Rubén,Tammaro, Alessandra,Schomakers, Bauke V.,Scantlebery, Angelique M. L.,Denis, Simone,Elfrink, Hyung L.,Giroud-Gerbetant, Judith,Cantó, Carles,López-Leonardo, Carmen,McIntyre, Rebecca L.,van Weeghel, Michel,Sánchez-Ferrer, álvaro,Houtkooper, Riekelt H.
, p. 1 - 17 (2021/03/22)
Nicotinamide adenine dinucleotide (NAD+) homeostasis is constantly compromised due to degradation by NAD+-dependent enzymes. NAD+ replenishment by sup-plementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.
Rhodamine-based fluorescent probe for sequential detection of Al3+ ions and adenosine monophosphate in water
Kaur, Rajinder,Saini, Sanjeev,Kaur, Navneet,Singh, Narinder,Jang, Doo Ok
, (2019/09/16)
Organic nanoparticles (N1) were prepared by dispersing thiophene-conjugated rhodamine derivative 1 in a buffer solution (10 mM TRIS, pH 7.4, containing 1% DMSO, v/v). N1 selectively recognized Al3+ ions through the “OFF-ON” switching mechanism of the spirolactam ring in rhodamine. The resulting N1·Al3+ complex recognized the biologically important molecule adenosine monophosphate (AMP) through a cation displacement process with a detection limit of 2 nM. N1 was capable of determining the concentration of Al3+ ions in environmental and biological samples. Portable test strips of N1 were prepared for the recognition of Al3+ ions and AMP for practical uses. Furthermore, it was demonstrated that the N1·Al3+ complex facilitated real-time monitoring of AMP concentration in the hydrolysis of ATP and ADP.
Intrinsic Apyrase-Like Activity of Cerium-Based Metal–Organic Frameworks (MOFs): Dephosphorylation of Adenosine Tri- and Diphosphate
Gu, Jinlou,Li, Chunzhong,Li, Ke,Yang, Jian
supporting information, p. 22952 - 22956 (2020/10/23)
Apyrase is an important family of extracellular enzymes that catalyse the hydrolysis of high-energy phosphate bonds (HEPBs) in ATP and ADP, thereby modulating many physiological processes and driving life activities. Herein, we report an unexpected discovery that cerium-based metal–organic frameworks (Ce-MOFs) of UiO-66(Ce) have intrinsic apyrase-like activity for ATP/ADP-related physiological processes. The abundant CeIII/CeIV couple sites of Ce-MOFs endow them with the ability to selectively catalyse the hydrolysis of HEPBs of ATP and ADP under physiological conditions. Compared to natural enzymes, they could resist extreme pH and temperature, and present a broad range of working conditions. Based on this finding, a significant inhibitory effect on ADP-induced platelet aggregation was observed upon exposing the platelet-rich plasma (PRP) to the biomimetic UiO-66(Ce) films, prefiguring their wide application potentials in medicine and biotechnology.
Production process of vidarabine monophosphate
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, (2019/01/23)
The invention belongs to the technical field of preparation of vidarabine monophosphate and particularly relates to a production process of vidarabine monophosphate. The production process of vidarabine monophosphate comprises the following steps of S1 dissolving vidarabine into organic solvent and cooling down the mixture; S2, adding in phosphoryl chloride to perform thermal reaction until that the residual content of the vidarabine is not higher than 3% of the added amount; S3, adding in palladium catalysts for catalytic reduction, then filtering reaction products, removing the solvent fromthe obtained filter liquor to obtain crude vidarabine monophosphate; S4, recrystallizing the crude vidarabine monophosphate obtained in S3 for purification. The production process of vidarabine monophosphate introduces the phosphoryl chloride relatively low in reactivity to react with the raw vidarabine, the reaction process is mild and easy to control, so that the produced quantity of side products can be reduced from the source; meanwhile, the novel palladium catalysts can selectively reduce introduced ether groups, thereby simplifying purification processes and achieving high product yieldand purity.
A Stark Contrast to Modern Earth: Phosphate Mineral Transformation and Nucleoside Phosphorylation in an Iron- and Cyanide-Rich Early Earth Scenario
Burcar, Bradley,Casta?eda, Alma,Lago, Jennifer,Daniel, Mischael,Pasek, Matthew A.,Hud, Nicholas V.,Orlando, Thomas M.,Menor-Salván, César
, p. 16981 - 16987 (2019/11/11)
Organophosphates were likely an important class of prebiotic molecules. However, their presence on the early Earth is strongly debated because the low availability of phosphate, which is generally assumed to have been sequestered in insoluble calcium and iron minerals, is widely viewed as a major barrier to organophosphate generation. Herein, we demonstrate that cyanide (an essential prebiotic precursor) and urea-based solvents could promote nucleoside phosphorylation by transforming insoluble phosphate minerals in a “warm little pond” scenario into more soluble and reactive species. Our results suggest that cyanide and its derivatives (metal cyanide complexes, urea, ammonium formate, and formamide) were key reagents for the participation of phosphorus in chemical evolution. These results allow us to propose a holistic scenario in which an evaporitic environment could concentrate abiotically formed organics and transform the underlying minerals, allowing significant organic phosphorylation under plausible prebiotic conditions.
Synthesis of Terminal Ribose Analogues of Adenosine 5′-Diphosphate Ribose as Probes for the Transient Receptor Potential Cation Channel TRPM2
Baszczyňski, Ond?ej,Watt, Joanna M.,Rozewitz, Monika D.,Guse, Andreas H.,Fliegert, Ralf,Potter, Barry V.L.
, p. 6143 - 6157 (2019/05/24)
TRPM2 (transient receptor potential cation channel, subfamily M, member 2) is a nonselective cation channel involved in the response to oxidative stress and in inflammation. Its role in autoimmune and neurodegenerative diseases makes it an attractive pharmacological target. Binding of the nucleotide adenosine 5′-diphosphate ribose (ADPR) to the cytosolic NUDT9 homology (NUDT9H) domain activates the channel. A detailed understanding of how ADPR interacts with the TRPM2 ligand binding domain is lacking, hampering the rational design of modulators, but the terminal ribose of ADPR is known to be essential for activation. To study its role in more detail, we designed synthetic routes to novel analogues of ADPR and 2′-deoxy-ADPR that were modified only by removal of a single hydroxyl group from the terminal ribose. The ADPR analogues were obtained by coupling nucleoside phosphorimidazolides to deoxysugar phosphates. The corresponding C2″-based analogues proved to be unstable. The C1″- and C3″-ADPR analogues were evaluated electrophysiologically by patch-clamp in TRPM2-expressing HEK293 cells. In addition, a compound with all hydroxyl groups of the terminal ribose blocked as its 1″-β-O-methyl-2″,3″-O-isopropylidene derivative was evaluated. Removal of either C1″ or C3″ hydroxyl groups from ADPR resulted in loss of agonist activity. Both these modifications and blocking all three hydroxyl groups resulted in TRPM2 antagonists. Our results demonstrate the critical role of these hydroxyl groups in channel activation.
RECOMBINANT SMNPP5 AND METHODS OF USE
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, (2019/10/04)
Described herein are methods and compositions for reducing coagulation, e.g., in a subject having a coagulation disease or disorder. Aspects of the invention relate to administering to a subject a recombinant SmNPP-5 protein or pharmaceutical composition described herein. Other aspects of the invention relate to methods for producing a recombinant SmNPP-5 protein.
