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991.
A Telomerase‐Responsive DNA Icosahedron for Precise Delivery of Platinum Nanodrugs to Cisplatin‐Resistant Cancer
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Yi Ma Zhaohui Wang Yuxuan Ma Zhihao Han Min Zhang Prof. Dr. Haiyan Chen Prof. Dr. Yueqing Gu 《Angewandte Chemie (International ed. in English)》2018,57(19):5389-5393
A telomerase‐responsive DNA icosahedron was designed to precisely release caged platinum nanodrugs into cisplatin‐resistance tumor cells for effective therapy. This DNA icosahedron was constructed from two pyramidal DNA cages connected with telomerase primers and telomeric repeats, and platinum nanodrugs were then encapsulated into the DNA structure. In the presence of telomerase, the primers are extended, leading to inner‐chain substitution of the DNA icosahedron and subsequent release of the caged nanodrugs. This DNA icosahedron can precisely release caged nanodrugs in response to telomerase in tumor cells, giving enhanced anticancer efficacy in drug‐resistant carcinoma and with reduced toxicity to normal tissues. We speculate that this precisely designed, well controlled DNA cage could be generalized to diverse anticancer drugs. 相似文献
992.
Inside Back Cover: Selective Inhibition of Lysine‐Specific Demethylase 5A (KDM5A) Using a Rhodium(III) Complex for Triple‐Negative Breast Cancer Therapy (Angew. Chem. Int. Ed. 40/2018)
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Guan‐Jun Yang Wanhe Wang Dr. Simon Wing Fai Mok Chun Wu Betty Yuen Kwan Law Dr. Xiang‐Min Miao Ke‐Jia Wu Dr. Hai‐Jing Zhong Prof. Dr. Chun‐Yuen Wong Prof. Dr. Vincent Kam Wai Wong Prof. Dr. Dik‐Lung Ma Prof. Dr. Chung‐Hang Leung 《Angewandte Chemie (International ed. in English)》2018,57(40):13349-13349
993.
Quantitative Prediction of Rate Constants for Aqueous Racemization To Avoid Pointless Stereoselective Syntheses
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Dr. Andrew Ballard Dr. Hiwa O. Ahmad Dr. Stefania Narduolo Lucy Rosa Nikki Chand Dr. David A. Cosgrove Dr. Peter Varkonyi Dr. Nabil Asaad Dr. Simone Tomasi Dr. Niklaas J. Buurma Dr. Andrew G. Leach 《Angewandte Chemie (International ed. in English)》2018,57(4):982-985
Racemization has a large impact upon the biological properties of molecules but the chemical scope of compounds with known rate constants for racemization in aqueous conditions was hitherto limited. To address this remarkable blind spot, we have measured the kinetics for racemization of 28 compounds using circular dichroism and 1H NMR spectroscopy. We show that rate constants for racemization (measured by ourselves and others) correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations. Such calculations thus provide predictions of the second‐order rate constants for general‐base‐catalyzed racemization that are usefully accurate. When applied to recent publications describing the stereoselective synthesis of compounds of purported biological value, the calculations reveal that racemization would be sufficiently fast to render these expensive syntheses pointless. 相似文献
994.
Dr. Jens Atzrodt Dr. Volker Derdau Prof. Dr. William J. Kerr Dr. Marc Reid 《Angewandte Chemie (International ed. in English)》2018,57(12):3022-3047
The various applications of hydrogen isotopes (deuterium, D, and tritium, T) in the physical and life sciences demand a range of methods for their installation in an array of molecular architectures. In this Review, we describe recent advances in synthetic C?H functionalisation for hydrogen isotope exchange. 相似文献
995.
An Efficient Method for the Conjugation of Hydrophilic and Hydrophobic Components by Solid‐Phase‐Assisted Disulfide Ligation
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Kyohei Muguruma Takuya Shirasaka Daichi Akiyama Dr. Kentarou Fukumoto Dr. Akihiro Taguchi Dr. Kentaro Takayama Dr. Atsuhiko Taniguchi Prof. Yoshio Hayashi 《Angewandte Chemie (International ed. in English)》2018,57(8):2170-2173
Chemical conjugation between hydrophilic and hydrophobic components is difficult because of their extremely different solubility. Herein, we report a new versatile method with a solid‐phase‐assisted disulfide ligation to overcome the difficulty of conjugation attributed to solubility. The method involves two steps in a one‐pot process: 1) loading of a hydrophobic molecule onto a resin in an organic solvent, and 2) release of the solid‐supported hydrophobic molecule as a conjugate with a hydrophilic molecule into an aqueous solvent. This strategy allows the use of a suitable solvent system for the substrates in each step. Conjugates of a water‐insoluble drug, plinabulin, with hydrophilic carriers that could not be prepared by solution‐phase reactions were obtained in moderate yields (29–45 %). This strategy is widely applicable to the conjugation of compounds with solubility problems. 相似文献
996.
《Journal of separation science》2018,41(8):1775-1780
The separation of polar compounds by high‐speed countercurrent chromatography is still regarded as a challenge. In this study, an efficient strategy for the separation of three polar compounds from Rheum tanguticum has been successfully conducted by using high‐speed countercurrent chromatography. X‐5 macroporous resin chromatography was used for the fast enrichment of the target compounds. Then, the target fraction was directly introduced into high‐speed countercurrent chromatography for separation using ethyl acetate/glacial acetic acid/water (100:1:100, v/v/v) as the solvent system. Consequently, three polar compounds including gallic acid, catechin, and gallic acid 4‐O‐β‐d ‐(6′‐O‐galloyl) glucoside were obtained with purities higher than 98%. The results showed glacial acetic acid could be such an appropriate regulator for the ethyl acetate/water system. This study provides a reference for the separation of polar compounds from natural products by high‐speed countercurrent chromatography. 相似文献
997.
《Journal of separation science》2018,41(5):1050-1062
Eucommiae Cortex is a classical traditional Chinese medicine, which needs to be processed by “sweating” methods. To select the suitable processing method and “sweating” processing condition for Eucommiae Cortex, in this study, the quality of Eucommiae Cortex was evaluated based on simultaneous determination of multiple bioactive constituents combined with gray relational analysis. The contents of lignans, iridoids, penylpropanoids, flavonoids, and phenols in samples were simultaneously determined using ultra‐fast performance liquid chromatography coupled with triple quadrupole‐linear ion trap tandem mass spectrometry. The chromatographic separation was performed on a Synergiۛ Hydro‐RP 100 Å column (100 mm × 2.0 mm, 2.5 μm) at 30°C with a gradient elution of acetonitrile with 0.1% formic acid/0.1% aqueous formic acid as the mobile phase. Furthermore, gray relational analysis was performed to evaluate and sort the samples according to the contents of 14 constituents by calculating the relative correlation degree of each sample. The results demonstrated that the quality of Eucommiae Cortex “sweating” at source area was better and the better “sweating” condition was to scrape off the cork layer before “sweating” with straw covering and sun drying. The developed method could provide the foundation and support for “sweating” processing method of Eucommiae Cortex in normalization and standardization. 相似文献
998.
《Journal of separation science》2018,41(12):2661-2671
Honey‐processed Astragalus, a widely used Qi‐tonifying and immunomodulating herb in traditional Chinese medicine, has strengthened the tonic effects and achieved fewer side effects compared with astragali radix in clinical application. Here, we focus on Qi‐tonifying biomarkers and pathways of honey‐processed Astragalus using urine metabolomics that provide the basis for building the linkage between metabolites in rat urine and its symptoms. The spleen Qi deficiency model group, normal group, astragali radix group, and honey‐processed Astragalus group were implemented to evaluate Qi‐tonifying effects. Twelve potential biomarkers were screened by multivariate statistical analysis by using ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry. Furthermore, pathways activity profiling showed unique pathways that are primarily involved in tryptophan metabolism, tricarboxylic acids cycle, and methionine metabolism. The results demonstrated that metabolomics coupled with pathway activity profiling were promising tools. It might serve as a novel methodological clue to systematically dissect the underlying Qi‐tonifying mechanism of honey‐processed Astragalus. 相似文献
999.
《Macromolecular bioscience》2018,18(7)
The cyclic brush polymers, due to the unique topological structure, have shown in the previous studies higher delivery efficacy than the bottlebrush analogues as carriers for drug and gene transfer. However, to the best of knowledge, the preparation of reduction‐sensitive cyclic brush polymers for drug delivery applications remains unexplored. For this purpose, a reduction‐sensitive amphiphilic cyclic brush copolymer, poly(2‐hydroxyethyl methacrylate‐g‐poly(ε‐caprolactone)‐disulfide link‐poly(oligoethyleneglycol methacrylate)) (P(HEMA‐g‐PCL‐SS‐POEGMA)) with reducible block junctions bridging the hydrophobic PCL middle layer and the hydrophilic POEGMA outer corona is designed and synthesized successfully in this study via a “grafting from” approach using sequential ring‐opening polymerization (ROP) and atom transfer free radical polymerization (ATRP) from a cyclic multimacroinitiator PHEMA. The resulting self‐assembled unimolecular core–shell–corona (CSC) micelles show sufficient salt stability and efficient destabilization in the intracellular reducing environment for a promoted drug release toward a greater therapeutic efficacy relative to the reduction‐insensitive analogues. The overall results demonstrate the reducible cyclic brush copolymers developed herein provides an elegant solution to the tradeoff between extracellular stability and intracellular high therapeutic efficacy toward efficient anticancer drug delivery. 相似文献
1000.
《Macromolecular bioscience》2018,18(7)
In two ABA type amphiphilic block copolymers (P1, P2), the hydrophobic B block consists of a bioreducible segmented poly(disulfide) (PDS), while poly‐N‐isopropylacrylamide (PNIPAM) or poly(triethyleneglycol)methylether‐methacrylate (PTEGMA) serve as the hydrophilic A blocks in P1 and P2, respectively, leading to the formation of polymersome and micelle, owing to the difference in the packing parameters. Both exhibit comparable doxorubicin (Dox) encapsulation efficiency, but glutathione (GSH) triggered release appears much faster from the polymersome than micelle owing to the complete degradation of the PDS segment in polymersome morphology unlike in micelle. Dox‐loaded polymers (P1‐Dox and P2‐Dox) exhibit minimum toxicity to normal cells like C2C12. By contrast, P1‐Dox shows excellent killing efficiency to the HeLa cells (cancer cell) (in which the GSH concentration is significantly higher). However, P2‐Dox reveals a rather poor activity even to HeLa cells. Fluorescence microscopy studies show comparable cellular uptake of P1‐Dox and P2‐Dox. But the polymersome entrapped dye escapes fast from the cargo and reach the nucleus, while the drug‐loaded micelle remains trapped in the perinuclear zone explaining the significant difference in the drug delivery performance of polymersome and micelle. 相似文献