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121.
122.
Dr. Divita Garg Gabriele Gabrieli Dr. Achim Stocker Dr. Tamis Darbre Prof. Dr. Jean‐Louis Reymond 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(50):17054-17063
The galactopeptide dendrimer GalAG2 ((β‐Gal‐OC6H4CO‐Lys‐Pro‐Leu)4(Lys‐Phe‐Lys‐Ile)2Lys‐His‐Ile‐NH2) binds strongly to the Pseudomonas aeruginosa (PA) lectin LecA, and it inhibits PA biofilms, as well as disperses already established ones. By starting with the crystal structure of the terminal tripeptide moiety GalA‐KPL in complex with LecA, a computational mutagenesis study was carried out on the galactotripeptide to optimize the peptide–lectin interactions. 25 mutants were experimentally evaluated by a hemagglutination inhibition assay, 17 by isothermal titration calorimetry, and 3 by X‐ray crystallography. Two of these tripeptides, GalA‐KPY (dissociation constant (KD)=2.7 μM ) and GalA‐KRL (KD=2.7 μM ), are among the most potent monovalent LecA ligands reported to date. Dendrimers based on these tripeptide ligands showed improved PA biofilm inhibition and dispersal compared to those of GalAG2 , particularly G2KPY ((β‐Gal‐OC6H4CO‐Lys‐Pro‐Tyr)4(Lys‐Phe‐Lys‐Ile)2Lys‐His‐Ile‐NH2). The possibility to retain and even improve the biofilm inhibition in several analogues of GalAG2 suggests that it should be possible to fine‐tune this dendrimer towards therapeutic use by adjusting the pharmacokinetic parameters in addition to the biofilm inhibition through amino acid substitutions. 相似文献
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124.
Dr. Daniel G. Silva Pim-Bart Feijens Rik Hendrickx An Matheeussen Lucie Grey Prof. Dr. Guy Caljon Prof. Dr. Louis Maes Prof. Dr. Flavio S. Emery Dr. Anna Junker 《ChemistryOpen》2021,10(9):922-927
This study identified the isoindolone ring as a scaffold for novel agents against Trypanosoma brucei rhodesiense and explored the structure-activity relationships of various aromatic ring substitutions. The compounds were evaluated in an integrated in vitro screen. Eight compounds exhibited selective activity against T. b. rhodesiense (IC50<2.2 μm ) with no detectable side activity against T. cruzi and Leishmania infantum. Compound 20 showed low nanomolar potency against T. b. rhodesiense (IC50=40 nm ) and no toxicity against MRC-5 and PMM cell lines and may be regarded as a new lead template for agents against T. b. rhodesiense. The isoindolone-based compounds have the potential to progress into lead optimization in view of their highly selective in vitro potency, absence of cytotoxicity and acceptable metabolic stability. However, the solubility of the compounds represents a limiting factor that should be addressed to improve the physicochemical properties that are required to proceed further in the development of in vivo-active derivatives. 相似文献
125.
In the past decades the topic of climate change has been subjected to intense scientific scrutiny, and since the mid-1990’s it has become an increasingly political issue. Because of increased temperatures and more frequent and intense extreme weather events, the number of direct injuries and deaths will increase, along with infectious diseases, whether food, water or vector-borne; respiratory and cardiovascular diseases are expected to rise due to worsened air pollution and extreme heat. In a context of on-going environmental degradation, local food-producing systems, both marine and terrestrial, will be affected and the risk of malnutrition, especially in children, will increase. These impacts on health and livelihood are expected to be significant factors in the spread of regional social crises, potentially leading to forced migration, conflicts and increased poverty. 相似文献
126.
Variable electron-phonon coupling in isolated metallic carbon nanotubes observed by Raman scattering
Wu Y Maultzsch J Knoesel E Chandra B Huang M Sfeir MY Brus LE Hone J Heinz TF 《Physical review letters》2007,99(2):027402
We report the existence of broad and weakly asymmetric features in the high-energy (G) Raman modes of freely suspended metallic carbon nanotubes of defined chiral index. A significant variation in peak width (from 12 cm(-1) to 110 cm(-1)) is observed as a function of the nanotube's chiral structure. When the nanotubes are electrostatically gated, the peak widths decrease. The broadness of the Raman features is understood as the consequence of coupling of the phonon to electron-hole pairs, the strength of which varies with the nanotube chiral index and the position of the Fermi energy. 相似文献
127.
Israël-Martyr Mbomekallé Bassem S. Bassil Andreas Suchopar Bineta Keita Louis Nadjo Malika Ammam Mohamed Haouas Francis Taulelle Ulrich Kortz 《Journal of Cluster Science》2014,25(1):277-285
We report on an improved synthesis and structural characterization of the cyclic 48-tungsto–8-arsenate(V) [H4As8W48O184]36? (1). The mixed lithium–potassium salt of this polyanion, K26.5Li9.5[H4As8W48O184]·90H2O (KLi-1), has been studied in the solid state by IR, single-crystal X-ray diffraction, and elemental analysis, and in solution by 183W NMR spectroscopy. 相似文献
128.
Rhodium‐Catalyzed Ketone Methylation Using Methanol Under Mild Conditions: Formation of α‐Branched Products
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Dr. Louis K. M. Chan Darren L. Poole Di Shen Dr. Mark P. Healy Prof. Timothy J. Donohoe 《Angewandte Chemie (International ed. in English)》2014,53(3):761-765
The rhodium‐catalyzed methylation of ketones has been accomplished using methanol as the methylating agent and the hydrogen‐borrowing method. The sequence is notable for the relatively low temperatures that are required and for the ability of the reaction system to form α‐branched products with ease. Doubly alkylated ketones can be prepared from methyl ketones and two different alcohols by using a sequential one‐pot iridium‐ and rhodium‐catalyzed process. 相似文献
129.
Damien Hueber Marie Hoffmann Dr. Benoît Louis Prof. Dr. Patrick Pale Dr. Aurélien Blanc 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(14):3903-3907
Gold(I)‐polyoxometalate hybrid complexes 1 – 4 ([PPh3AuMeCN]xH4?xSiW12O40, x=1–4) were synthesized and characterized. The structure of the primary gold(I)–polyoxometalate 1 (x=1) was fully ascertained by XRD, FTIR, 31P and 29Si magic‐angle spinning (MAS) NMR, mass spectroscopy, and SEM–energy dispersive X‐ray spectroscopy (EDX) techniques. Moreover, this complex exhibited better catalytic activity and selectivity compared with standard, homogeneous, gold catalysts in the new rearrangement of propargylic gem‐diesters. 相似文献
130.
Synthesis and Biological Evaluation of a Class of Mitochondrially‐Targeted Gadolinium(III) Agents
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Dr. Daniel E. Morrison Dr. Jade B. Aitken Dr. Martin D. de Jonge Dr. Fatiah Issa Prof. Hugh H. Harris Prof. Louis M. Rendina 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(50):16602-16612
A structure–activity relationship study of a library of novel bifunctional GdIII complexes covalently linked to arylphosphonium cations is reported. Such complexes have been designed for potential application in binary cancer therapies such as neutron capture therapy and photon activation therapy. A positive correlation was found between lipophilicity and cytotoxicity of the complexes. Mitochondria uptake was determined by means of inductively coupled plasma mass spectrometry (ICP‐MS), and Gd uptake was determined by means of quantification using synchrotron X‐ray fluorescence (XRF) imaging. A negative correlation between lipophilicity and tumour selectivity of the GdIII complexes was demonstrated. This study highlights the delicate balance required to minimise in vitro cytotoxicity and optimise in vitro tumour selectivity and mitochondrial localisation for this new class of mitochondrially‐targeted binary therapy agents. We also report the highest in vitro tumour selectivity for any Gd agent reported to date, with a T/N (tumour/normal cell) ratio of up to 23.5±6.6. 相似文献