Oligonucleotide therapeutics have transformative potential in modern medicine but are poor drug candidates in themselves unless fitted with compensatory carrier systems. We describe a simple approach ...to transform a designed porous protein cage into a nucleic acid delivery vehicle. By introducing arginine mutations to the lumenal surface, a positively supercharged capsule is created, which can encapsidate oligonucleotides in vitro with high binding affinity. We demonstrate that the siRNA-loaded cage is taken up by mammalian cells and releases its cargo to induce RNAi and knockdown gene expression. These general concepts could also be applied to alternative scaffold designs, expediting the development of artificial protein cages toward delivery applications.
Actiniae‐like carbon nitride (ACN) bundles were synthesized by the pyrolysis of an asymmetric supramolecular precursor prepared from L‐arginine (L‐Arg) and melamine. ACN has adjustable band gaps ...(2.25 eV–2.75 eV) and hollow microtubes with ultrathin pore walls, which enrich reaction sites, improve visible‐light absorption and enhance charge separation. In the presence of phenylcarbinol, ACN exhibited excellent water‐splitting ability (95.3 μmol h−1) and in the meanwhile phenylcarbinol was selectively oxidized to benzaldehyde (conversion of 90.9 %, selectivity of 99.7 %) under solar irradiation. For the concurrent reactions, 2D isotope labeling, separation, and detection were conducted to confirm that the proton source of released hydrogen is water. The mechanism of water splitting and phenylcarbinol oxidation was also investigated.
Ultrathin porous carbon nitride bundles were designed based on the pyrolysis of asymmetric supramolecular precursor from L‐arginine and melamine. It has a high specific surface area and adjustable band gap. Through the coupling of water‐splitting and phenylcarbinol oxidation, the efficiency of hydrogen evolution was promoted and phenylcarbinol oxidation was activated.
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an ascendant class of natural products with diverse structures and functions. Recently, we identified a wide array of ...RiPP gene clusters that are regulated by quorum sensing and encode one or more radical S-adenosylmethionine (RaS) enzymes, a diverse protein superfamily capable of catalyzing chemically difficult transformations. In this work, we characterize a novel reaction catalyzed by one such subfamily of RaS enzymes during RiPP biosynthesis: installation of a macrocyclic carbon–carbon bond that links the unactivated δ-carbon of an arginine side chain to the ortho-position of a tyrosine-phenol. Moreover, we show that this transformation is, unusually for RiPP biogenesis, largely insensitive to perturbations of the leader portion of the precursor peptide. This reaction expands the already impressive scope of RaS enzymes and contributes a unique macrocyclization motif to the growing body of RiPP architectures.
Solidified natural gas (SNG) is a promising option to store natural gas in the form of clathrate hydrates because of several benefits offered that include high degree of safety, eco-friendliness, ...high volumetric storage capacity, and the relative ease of gas recovery. Environmentally benign amino acids have been reported as promising kinetic promoters for enhancing methane hydrate formation. In this work, we examine in detail the effect of three different types of amino acidstryptophan (nonpolar, hydrophobic amino acid with aromatic side chain), histidine (polar, basic amino acid with aromatic side chain), and arginine (polar, basic amino acid with aliphatic side chain)on the kinetics of methane hydrate formation. The effect of amino acid concentration on the hydrate formation kinetics was investigated in two reactor configurations, namely, stirred and unstirred tank reactors. Amongst the amino acids studied, the best kinetic promotion for methane hydrate formation (in both stirred and unstirred reactor configurations) was achieved by tryptophan. The optimal concentration for best kinetic promotion of methane hydrate formation varies with the amino acid for same operating conditions. It may be inferred that the presence of an aromatic side chain and hydrophobic nature resulted in a better enhancement of methane hydrate formation.
Glucose is a key energy supplier and nutrient for tumor growth. Herein, inspired by the glucose oxidase (GOx)‐assisted conversion of glucose into gluconic acid and toxic H2O2, a novel treatment ...paradigm of starving‐like therapy is developed for significant tumor‐killing effects, more effective than conventional starving therapy by only cutting off the energy supply. Furthermore, the generated acidic H2O2 can oxidize l‐Arginine (l‐Arg) into NO for enhanced gas therapy. By using hollow mesoporous organosilica nanoparticle (HMON) as a biocompatible/biodegradable nanocarrier for the co‐delivery of GOx and l‐Arg, a novel glucose‐responsive nanomedicine (l‐Arg‐HMON‐GOx) has been for the first time constructed for synergistic cancer starving‐like/gas therapy without the need of external excitation, which yields a remarkable H2O2–NO cooperative anticancer effect with minimal adverse effect.
Synergistic therapy: A biocompatible and biodegradable nanomedicine based on glucose oxidase/l‐arginine co‐loaded hollow mesoporous organosilica nanoparticles has been successfully constructed for converting intratumoral glucose into high concentrations of toxic hydrogen peroxide and nitric oxide. An endogenous synergistic cancer therapy for efficient tumor eradication has been developed.
Sestrin2 is a leucine sensor for the mTORC1 pathway Wolfson, Rachel L.; Chantranupong, Lynne; Saxton, Robert A. ...
Science (American Association for the Advancement of Science),
01/2016, Letnik:
351, Številka:
6268
Journal Article
Recenzirano
Odprti dostop
Leucine is a proteogenic amino acid that also regulates many aspects of mammalian physiology, in large part by activating the mTOR complex 1 (mTORC1) protein kinase, a master growth controller. Amino ...acids signal to mTORC1 through the Rag guanosine triphosphatases (GTPases). Several factors regulate the Rags, including GATOR1, a GTPase-activating protein; GATOR2, a positive regulator of unknown function; and Sestrin2, a GATOR2-interacting protein that inhibits mTORC1 signaling. We find that leucine, but not arginine, disrupts the Sestrin2-GATOR2 interaction by binding to Sestrin2 with a dissociation constant of 20 micromolar, which is the leucine concentration that half-maximally activates mTORC1. The leucine-binding capacity of Sestrin2 is required for leucine to activate mTORC1 in cells. These results indicate that Sestrin2 is a leucine sensor for the mTORC1 pathway.
•Photocatalysts of g-C3N4/TiO2 nanosheets was synthesized by a facile biomimetic method for the first time.•Heterojunction between TiO2 and g-C3N4 promotes the separation of photo-generated ...carriers.•The large surface area of nanosheets and small size of TiO2 nanoparticle improve the photoactivity.•The synthetic procedure of g-C3N4/TiO2 nanosheets was illustrated.
A facile and efficient approach was first developed to prepare g-C3N4/TiO2 nanocomposites by combining the arginine-enabled biomimetic mineralization of TiO2 with the thermal oxidation etching of bulk g-C3N4. The resultant g-C3N4/TiO2 nanocomposites exhibit a well-defined morphology, in which TiO2 nanoparticles about 5.5nm in diameter are uniformly distributed on the g-C3N4 nanosheet. They exhibit higher degradation efficiency for Rhodamine B (RhB) than TiO2, g-C3N4 and their mixture under visible light and simulated-sunlight irradiation. In all the as-prepared samples, the g-C3N4/TiO2 nanosheet with 25.9wt% of g-C3N4 exhibits the highest photocatalytic efficiency, which can degrade almost all RhB under simulated-sunlight irradiation within 50min. The synergistic effect between TiO2 and g-C3N4 plays an important role for the enhanced photocatalytic activity of g-C3N4/TiO2 nanosheets. This kind of sheet-like nanocomposites may find the potential application for the photocatalytic degradation of organic pollutants.
In the present work, we have successfully developed 2-amino-5-guanidinopentanoic acid modified activated carbon (AGDPA@AC) for the effective removal of methylene blue (MB) dye from aqueous medium. ...The AGDPA@AC was characterized using different instrumental techniques viz., SEM, EDX, FTIR, TGA and zeta potential. The influence of different parameters viz. pH, initial MB concentration, contact time and temperature on the adsorption capacity was investigated. The maximum adsorption capacity of MB of on AGDPA@AC was found at pH 8 and 120 min. The maximum Langmuir adsorption capacity of AGDPA@AC was 219.9 mg/g at 25 °C. The adsorption followed Langmuir isotherm and pseudo-second order kinetic models well. The result of thermodynamic data showed that the adsorption was spontaneous and exothermic in nature. The binding of MB dye onto AGDPA@AC surface was through electrostatic interactions. Regeneration studies indicated that the adsorbent could successfully retain MB, even after four cycles. The adsorption percent of AGDPA@AC for MB dye was 75% even after four adsorption-desorption cycles.
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•Arginine based composite (AGDPA@AC) was synthesized.•MB dye was efficiently removed using AGDPA@AC.•AGDPA@AC exhibited high adsorption capacity for MB dye.•The mechanism of adsorption was electrostatic interaction and π-π interaction.
A novel concept to improve the catalytic functions of nucleic acids (DNAzymes) is introduced. The method involves the conjugation of a DNA recognition sequence (aptamer) to the catalytic DNAzyme, ...yielding a hybrid structure termed “nucleoapzyme”. Concentrating the substrate within the “nucleoapzyme” leads to enhanced catalytic activity, displaying saturation kinetics. Different conjugation modes of the aptamer/DNAzyme units and the availability of different aptamer sequences for a substrate provide diverse means to design improved catalysts. This is exemplified with (i) The H2O2-mediated oxidation of dopamine to aminochrome using a series of hemin/G-quadruplex-dopamine aptamer nucleoapzymes. All nucleoapzymes reveal enhanced catalytic activities as compared to the separated DNAzyme/aptamer units, and the most active nucleoapzyme reveals a 20-fold enhanced activity. Molecular dynamics simulations provide rational assessment of the activity of the various nucleoapzymes. The hemin/G-quadruplex–aptamer nucleoapzyme also stimulates the chiroselective oxidation of l- vs d-DOPA by H2O2. (ii) The H2O2-mediated oxidation of N-hydroxy-l-arginine to l-citrulline by a series of hemin/G-quadruplex–arginine aptamer conjugated nucleoapzymes.
Hydrogenases are metalloenzymes that catalyze the conversion of protons and molecular hydrogen, H2. FeFe-hydrogenases show particularly high rates of hydrogen turnover and have inspired numerous ...compounds for biomimetic H2 production. Two decades of research on the active site cofactor of FeFe-hydrogenases have put forward multiple models of the catalytic proceedings. In comparison, our understanding of proton transfer is poor. Previously, residues were identified forming a hydrogen-bonding network between active site cofactor and bulk solvent; however, the exact mechanism of catalytic proton transfer remained inconclusive. Here, we employ in situ infrared difference spectroscopy on the FeFe-hydrogenase from Chlamydomonas reinhardtii evaluating dynamic changes in the hydrogen-bonding network upon photoreduction. While proton transfer appears to be impaired in the oxidized state (Hox), the presented data support continuous proton transfer in the reduced state (Hred). Our analysis allows for a direct, molecular unique assignment to individual amino acid residues. We found that transient protonation changes of glutamic acid residue E141 and, most notably, arginine R148 facilitate bidirectional proton transfer in FeFe-hydrogenases.
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