Azoles are five-membered heterocycles often found in the backbones of peptidic natural products and synthetic peptidomimetics. Here, we report a method of ribosomal synthesis of azole-containing ...peptides involving specific ribosomal incorporation of a bromovinylglycine derivative into the nascent peptide chain and its chemoselective conversion to a unique azole structure. The chemoselective conversion was achieved by posttranslational dehydrobromination of the bromovinyl group and isomerization in aqueous media under fairly mild conditions. This method enables us to install exotic azole groups, oxazole and thiazole, at designated positions in the peptide chain with both linear and macrocyclic scaffolds and thereby expand the repertoire of building blocks in the mRNA-templated synthesis of designer peptides.
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•Novel 18F-labeling reagent 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) 18Ffluorobenzene (18FTDBFB) was developed.•Simply and rapid synthesis of 18FTDBFB was performed compared ...with a previous report on 18Ffluorophenylboronic acid.•The Suzuki coupling of 18FTDBFB using microwave heating yielded 4-18Ffluorobiphenyl and 18Fpitavastatin derivative.•18FTDBFB obtained by rapid synthesis has the usefulness as an indirect 18F-labeling reagent.
Indirect 18F labeling methods using 18F-containing compounds such as N-succinimidyl-4-18Ffluorobenzoate and 4-18Ffluoroiodobenzene as labeling reagents have been reported because direct 18F labeling has difficulty in labeling aromatic compounds. In this study, we synthesized the 18F-labeling reagent 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) 18Ffluorobenzene (18FTDBFB) using a resonant-type microwave reactor in the presence of (2,2,6,6-tetramethylpiperidine 1-oxyl and a copper catalyst. Compared with a previous report on 18Ffluorophenylboronic acid, 18FTDBFB was synthesized simply. Moreover, we applied 18FTDBFB for the Suzuki coupling with triflate and bromide precursors. The Suzuki coupling of 18FTDBFB and precursors using resonant-type microwave reactor yielded 4-18Ffluorobiphenyl and the 18Fpitavastatin derivative as the coupling products. These results show the potential of 18FTDBFB obtained using rapid synthesis as an indirect 18F-labeling reagent.
In one-dimensional systems with partially filled valence bands, simultaneous changes occur in the electronic states and crystal structures. This is known as the Peierls transition. The Peierls ...transition (cation dimerization) in VO2, which has a quasi-one-dimensional structure, is well-known, and its mechanism has been extensively discussed. Honeycomb lattices exhibit the Peierls instability owing to their low dimensionality. However, cation dimerization is rare in the 3d1 honeycomb lattice system. Here, we perform an in-depth examination of the V–V dimerization (formation of V–V direct bond) in ilmenite-type MgVO3, which is a 3d1 honeycomb lattice system. A ladderlike pattern was observed in the V–V dimers through synchrotron X-ray experiments at temperatures below 500 K. This dimerization was accompanied by a magnetic-to-nonmagnetic transition. Moreover, a valence bond liquid phase may exist at 500–600 K. Our results reveal the behavior of the valence electrons in the 3d1 honeycomb lattice system.
Two enzymes are considered to be unique to the photosynthetic Calvin-Benson cycle: ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), responsible for CO
fixation, and phosphoribulokinase ...(PRK). Some archaea possess bona fide RuBisCOs, despite not being photosynthetic organisms, but are thought to lack PRK. Here we demonstrate the existence in methanogenic archaea of a carbon metabolic pathway involving RuBisCO and PRK, which we term 'reductive hexulose-phosphate' (RHP) pathway. These archaea possess both RuBisCO and a catalytically active PRK whose crystal structure resembles that of photosynthetic bacterial PRK. Capillary electrophoresis-mass spectrometric analysis of metabolites reveals that the RHP pathway, which differs from the Calvin-Benson cycle only in a few steps, is active in vivo. Our work highlights evolutionary and functional links between RuBisCO-mediated carbon metabolic pathways in methanogenic archaea and photosynthetic organisms. Whether the RHP pathway allows for autotrophy (that is, growth exclusively with CO
as carbon source) remains unknown.
It has been well established that the ribosome can accept various nucleophiles on the Xacyl-tRNA in the A site during elongation, where X can be amino, N-alkyl-amino, hydroxy, and thiol groups. ...However, it remains elusive that the ribosome is able to accept an electrophile in the P site other than the carboxyl group during elongation. Here we report ribosomal formation of a thioamide bond in the mRNA-dependent polypeptide synthesis. In this study, amino(carbothio)acyl-tRNA was prepared by flexizyme and used for the expression of peptides containing a thioamide bond in the nascent peptide chain. We give strong evidence that the thioamide-peptide was formed but accompanied by the amide counterpart due to rapid carbo(S-to-O) exchange during the preparation of amino(carbothio)acyl-tRNA. We also demonstrate the ribosomal formation of thioamide and N-methyl-thioamide bonds in linear as well as macrocyclic peptide scaffolds in the mRNA-dependent manner, showing its potential for applications in peptide-based drug discovery and studying peptide/protein structure and function.
Abstract Radioprotective agents have been developed to protect patients against the damaging and lethal effects of ionizing radiation. However, in addition to the intrinsic ability to target reactive ...oxygen species (ROS), the ability to retain a significant level of bioavailability is desirable in radioprotective agents because that would increase and prolong their radioprotective efficacy and improve its safety. Here, we report the development of a novel nanoparticle-based radioprotective agent with improved bioavailability, which suppressed the adverse effects typically associated with low-molecular-weight (LMW) antioxidants. We developed biocompatible and colloidally stable nanoparticles in which nitroxide radicals that were covalently conjugated (redox nanoparticles, RNPN ) effectively scavenged radiation-induced ROS with a characteristically prolonged bioavailability and tissue-residence time compared with that of conventional LMW antioxidants. The confinement of the nitroxide radicals in the RNPN core prevented its rapid metabolism and excretion out of the body. The nano-sized formulation prevented internalization of RNPN in healthy cells, thereby preserving the normal function of the redox reactions in the cell. This improved pharmacological performance dramatically reduced the radiation-induced organ dysfunctions and increased the survival time of the lethally irradiated mice when the nanoparticles were administered 3–24 h before whole-body irradiation.
Enzyme-modified lecithin that contains lysophosphatidylcholine (LPC) is generally recognized as safe. However, its potential as a functional ingredient has been less investigated than other choline ...(Ch)-containing compounds, such as glycerophosphocholine (GPC). Reports on the possibility of LPC functioning as a cholinergic precursor in vivo and on its kinetics are limited to docosahexaenoic acid-bound LPC. Herein, three experiments were performed to investigate these processes in scopolamine (SCO)-treated rats. First, an egg-derived LPC reagent was orally administered to rats, and brain acetylcholine (ACh), Ch, plasma Ch, and LPC were measured. Second, soy- and rapeseed-derived enzyme-modified lecithins and GPC were administered for comparison. Third, soy-derived enzyme-modified lecithins with different fat contents were administered for comparison. The LPC reagent mitigated SCO-induced ACh depletion at 500 mg/kg body weight and increased plasma Ch, but not LPC, concentrations. Additionally, soy-derived LPC-containing food additive counteracted brain ACh depletion similarly to GPC. Interestingly, plasma Ch and linoleoyl-LPC levels were higher when soy-derived LPC with a higher fat content was administered, whereas the plasma levels of palmitoyl-LPC decreased and those of total LPC remained constant. In conclusion, egg- and soy-derived LPC species function as cholinergic precursors in vivo, and future studies should explore this potential.
Abstract
Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted ...imaging, especially positron emission tomography (PET), has emerged. Although various radiolabeled GLP-1R agonist exendin-4-based probes with chemical modifications for PET imaging have been investigated, an optimal candidate probe and its scanning protocol remain a necessity. Thus, we investigated the utility of a novel exendin-4-based probe conjugated with polyethylene glycol (PEG) for
18
FFB(ePEG12)12-exendin-4 PET imaging for insulinoma detection. We utilized
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FFB(ePEG12)12-exendin-4 PET/CT to visualize mouse tumor models, which were generated using rat insulinoma cell xenografts. The probe demonstrated high uptake value on the tumor as 37.1 ± 0.4%ID/g, with rapid kidney clearance. Additionally, we used
Pdx1-Cre;Trp53
R172H
;Rb
f/f
mice, which developed endogenous insulinoma and glucagonoma, since they enabled differential imaging evaluation of our probe in functional pancreatic neuroendocrine neoplasms. In this model, our
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FFB(ePEG12)12-exendin-4 PET/CT yielded favorable sensitivity and specificity for insulinoma detection. Sensitivity: 30-min post-injection 66.7%, 60-min post-injection 83.3%, combined 100% and specificity: 30-min post-injection 100%, 60-min post-injection 100%, combined 100%, which was corroborated by the results of in vitro time-based analysis of internalized probe accumulation. Accordingly,
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FFB(ePEG12)12-exendin-4 is a promising PET imaging probe for visualizing insulinoma.
Previous reports have shown that during chronic inflammation, the tryptophan (TRP)-kynurenine (KYN) pathway plays a pivotal role in the onset of depression. The aim of this study was to investigate ...the characteristics of the serum TRP-KYN pathway metabolite profile in high-risk subjects of major depressive disorder (HRMDD) defined by depression scores. The concentrations of TRP-KYN pathway metabolites {TRP, KYN, 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), kynurenic acid (KYNA) and anthranilic acid (AA)} were assessed in serum from HRMDD, chronic pain disorder patients and healthy controls. In serum from HRMDD, elevated levels of AA and decreased levels of TRP were observed, but the levels of other metabolites were not changed. Furthermore, the change in the AA
/AA
ratio in subjects who progressed from a health. y state to a depressive state was correlated with an increase in the CES-D score. The level of IL-1 receptor antagonist (IL-1RA) was negatively correlated with that of AA. Interestingly, we confirmed AA as a possible biomarker for depression-related symptoms, since the metabolite profiles in the chronic pain disorder group and chronic unpredictable mild stress model mice were similar to those in the HRMDD. These results suggest that AA may be an effective marker for HRMDD.
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![Novel synthesis of an [18F]...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0040-4039/small "Novel synthesis of an [18F]aryl boronic acid ester as a reagent for 18F-labeling via Suzuki coupling")
