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All total 137 Articles be found
All total 137 Articles be foundDynamic 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.
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.
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.
