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61.
Thomas Marmin Prof. Yves L. Dory 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(27):6707-6711
Cyclohexane and cyclotri-β-alanyl have been used as scaffolds for the design of new C3-symmetric rings incorporating conjugated alkenes and dienes. All three C3-symmetric lactams share the same triangular shape and their crystal system is trigonal. They all belong to the R3 space group, R3m, R3 and R3c, for the increasingly large 12-, 18- and 24-membered rigid rings, respectively. All lactams stack on top of each other, through H-bonds and van der Waals noncovalent interactions, leading to endless supramolecular cylinders and tubes. The largest member of the family leads to tubes, the central pores of which is wide enough to let water in. A common feature of all the lactams is their very large dipole, of around 9 D, according to DFT calculations. Surprisingly, all the resulting cylinders and tubes pack side by side in the crystals, with all the dipoles pointing to the same direction. As a result, all three crystals are anisotropic and appear to be the first members of a new kind of highly polar crystals. 相似文献
62.
63.
J. Conrad J. Cohen-Tanugi L. E. Strigari 《Journal of Experimental and Theoretical Physics》2015,121(6):1104-1135
The launch of the gamma-ray telescope Fermi Large Area Telescope (Fermi-LAT) started a pivotal period in indirect detection of dark matter. By outperforming expectations, for the first time a robust and stringent test of the paradigm of weakly interacting massive particles (WIMPs) is within reach. In this paper, we discuss astrophysical targets for WIMP detection and the challenges they present, review the analysis tools which have been employed to tackle these challenges, and summarize the status of constraints on and the claimed detections in the WIMP parameter space. Methods and results will be discussed in comparison to Imaging Air Cherenkov Telescopes. We also provide an outlook on short term and longer term developments. 相似文献
64.
Kondakov N. N. Mel´nikova T. M. Chekryzhova T. V. Mel´nikova M. V. Zinin A. I. Torgov V. I. Chizhov A. O. Kononov L. O. 《Russian Chemical Bulletin》2015,64(5):1142-1148
Russian Chemical Bulletin - Terminal disaccharide fragment of phenolic glycolipid from Mycobacterium leprae (PGL-I) was synthesized as a glycoside with 4-(2-aminoethoxy)phenyl aglycon. The obtained... 相似文献
65.
Claudia Poloni Marc C. A. Stuart Pieter van der Meulen Wiktor Szymanski Ben L. Feringa 《Chemical science》2015,6(12):7311-7318
The external photocontrol over peptide folding, by the incorporation of molecular photoswitches into their structure, provides a powerful tool to study biological processes. However, it is limited so far to switches that exhibit only a rather limited geometrical change upon photoisomerization and that show thermal instability of the photoisomer. Here we describe the use of an overcrowded alkene photoswitch to control a model β-hairpin peptide. This photoresponsive unit undergoes a large conformational change and has two thermally stable isomers which has major influence on the secondary structure and the aggregation of the peptide, permitting the phototriggered formation of amyloid-like fibrils. 相似文献
66.
Briana L. Simms Nan Ji Indika Chandrasiri Mohammad Farid Zia Chinwe S. Udemgba Ravinder Kaur Jared H. Delcamp Alex Flynt Chalet Tan Davita L. Watkins 《Journal of polymer science. Part A, Polymer chemistry》2021,59(19):2177-2192
Here, we demonstrate the applicability of self-assembling linear-dendritic block copolymers (LDBCs) and their nanoaggregates possessing varied surfaces as therapeutic nanocarriers. These LDBCs are comprised of a hydrophobic, linear polyester chemically coupled to a hydrophilic dendron polyamidoamine (PAMAM)—the latter of which acts as the surface of the self-assembled nanoaggregate in aqueous media. To better understand how surface charge density affects the overall operability of these nanomaterials, we modified the nanoaggregate surface to yield cationic (NH3+), neutral (OH), and anionic (COO−) surfaces. The effect of these modifications on the physicochemical properties (i.e., size, morphology, and surface charge density), colloidal stability, and cellular uptake mechanism of the polymeric nanocarrier were investigated. This comparative study demonstrates the viability of nanoaggregates formed from PDLLA-PAMAM LDBCs to serve as nanocarriers for applications in drug delivery. 相似文献
67.
68.
Chris H. Hill Agnete H. Viuff Samantha J. Spratley Stéphane Salamone Stig H. Christensen Randy J. Read Nigel W. Moriarty Henrik H. Jensen Janet E. Deane 《Chemical science》2015,6(5):3075-3086
Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease. 相似文献
69.
70.
Natalia L. Calvo Sebastian O. SimonettiRubén M. Maggio Teodoro S. Kaufman 《Analytica chimica acta》2015
Exposure of cimetidine (CIM) to dry heat (160–180 °C) afforded, upon cooling, a glassy solid containing new and hitherto unknown products. The kinetics of this process was studied by a second order chemometrics-assisted multi-spectroscopic approach. Proton and carbon-13 nuclear magnetic resonance (NMR), as well as ultraviolet and infrared spectroscopic data were jointly used, whereas multivariate curve resolution with alternating least squares (MCR-ALS) was employed as the chemometrics method to extract process information. It was established that drug degradation follows a first order kinetics. 相似文献