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991.
Christopher Selleck Prof. James A. Larrabee Assoc. Prof. Jeffrey Harmer Assoc. Prof. Luke W. Guddat Dr. Nataša Mitić Waleed Helweh Prof. David L. Ollis Dr. Whitney R. Craig Prof. David L. Tierney Dr. Marcelo Monteiro Pedroso Prof. Gerhard Schenk 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(49):17704-17714
Antibiotic resistance has emerged as a major threat to global health care. This is largely due to the fact that many pathogens have developed strategies to acquire resistance to antibiotics. Metallo‐β‐lactamases (MBL) have evolved to inactivate most of the commonly used β‐lactam antibiotics. AIM‐1 is one of only a few MBLs from the B3 subgroup that is encoded on a mobile genetic element in a major human pathogen. Here, its mechanism of action was characterised with a combination of spectroscopic and kinetic techniques and compared to that of other MBLs. Unlike other MBLs it appears that AIM‐1 has two avenues available for the turnover of the substrate nitrocefin, distinguished by the identity of the rate‐limiting step. This observation may be relevant with respect to inhibitor design for this group of enzymes as it demonstrates that at least some MBLs are very flexible in terms of interactions with substrates and possibly inhibitors. 相似文献
992.
Eva‐Maria Christ Sophie S. Müller Elena Berger‐Nicoletti Holger Frey 《Journal of polymer science. Part A, Polymer chemistry》2014,52(19):2850-2859
Synthesis and characterization of novel hydroxyl‐functionalized oxetane‐inimers with varied alkyl chain length—3‐hydroxymethyl‐3‐methoxymethyloxetane, 3‐hydroxymethyl‐3‐propoxymethyloxetane, and 3‐hexoxymethyl‐3‐hydroxymethyloxetane—is reported. Cationic ring‐opening polymerization of these latent, cyclic AB2‐monomers leads to hyperbranched (hb) polyether polyols with degrees of branching between 34 and 69%, confirmed by inverse‐gated (IG) 13C NMR spectroscopy. The hyperbranching polymerization yielded apparent molecular weights (Mn) ranging from 500 to 2500 g mol?1 (size exclusion chromatography). Remarkably, by copolymerization of 1,1,1‐tris(4‐hydroxyphenyl)ethane as a “focal” unit, polymerization under slow monomer addition conditions lead to higher apparent molecular weights up to 11,220 g mol?1. The end groups of the hb polymers were studied via matrix‐assisted laser desorption/ionization time of flight mass and NMR spectrometry. By varying the alkyl chain length, tailoring of the solubility and glass transition temperatures of the materials is possible. Potential applications range from macroinitiators with defined polarity to tailoring of surface properties of antifouling materials. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2850–2859 相似文献
993.
Raja Mukherjee Sayantan Mondal Dr. Amit Basak Dibyendu Mallick Dr. Eluvathingal D. Jemmis 《化学:亚洲杂志》2012,7(5):957-965
The preference for Garratt–Braverman (GB) over Myers–Saito (MS) and Schmittel (SCM) cyclizations has recently been demonstrated in sulfones capable of undergoing all three of the processes. As the GB cyclization is a self-quenching process, there is a need to change the selectivity to the non-self-quenching MS or SCM pathway so as to enhance the DNA-cleaving efficiency that operates through the radical-mediated process. Herein we report a conformational constraint-based strategy developed by using computations (M06-2X/6-31+G*) to switch the selectivity from GB to MS/SCM pathway which also results in greater DNA-cleavage activity. The preference for GB could be brought back by easing the constraint with the help of spacers. 相似文献
994.
Xiaojing Lai Jing Liu Xin Xu Jie Li Baojun Zhang Lijun Wei Hongping Cai Xianglei Cheng 《Journal of separation science》2020,43(2):398-405
In reversed‐phase liquid chromatography, tetracycline antibiotics yield broad and asymmetrical peaks, as a result of their ionic interaction with the anionic free silanol groups and metal ion present in the silica‐based stationary phases (commonly derivatized with C18 groups). These frequently encountered difficulties were absolutely eliminated based on dual effect when methanesulfonic acid was employed as an eluent additive. The study revealed that the performance of methanesulfonic acid to minimize the “silanol effect” is mainly explained by both direct neutralization of the anionic silanol sites and electrostatic attraction with analytes. Based on these dual action mechanisms, an ultrasensitive method has been successfully developed for the simultaneous determination of tetracycline antibiotics and their derivatives (minocycline, oxytetracycline, tetracycline, chlortetracycline, metacycline, doxycycline, 4‐epitetracycline, and 4‐epichlortetracycline) in bovine milk with convenient ultraviolet detection within 15 min. Under the optimal conditions, the calibration curves showed good linearity (r2 > 0.999) for all analytes in the range of 1~200 ng/mL with the instrument limits of detection as low as 0.3 ng/mL. The study sheds new light on suitable additives to analyze basic compounds with the advantage of good compatibility with MS detection. 相似文献
995.
Bee-Ha Gan Xingguang Cai Sacha Javor Thilo Khler Jean-Louis Reymond 《Molecules (Basel, Switzerland)》2020,25(23)
There is an urgent need to develop new antibiotics against multidrug-resistant bacteria. Many antimicrobial peptides (AMPs) are active against such bacteria and often act by destabilizing membranes, a mechanism that can also be used to permeabilize bacteria to other antibiotics, resulting in synergistic effects. We recently showed that G3KL, an AMP with a multibranched dendritic topology of the peptide chain, permeabilizes the inner and outer membranes of Gram-negative bacteria including multidrug-resistant strains, leading to efficient bacterial killing. Here, we show that permeabilization of the outer and inner membranes of Pseudomonas aeruginosa by G3KL, initially detected using the DNA-binding fluorogenic dye propidium iodide (PI), also leads to a synergistic effect between G3KL and PI in this bacterium. We also identify a synergistic effect between G3KL and six different antibiotics against the Gram-negative Klebsiella pneumoniae, against which G3KL is inactive. 相似文献
996.
Dr. Chunhua Zhao Dr. Shan Yan Qin Li Dr. Hucheng Zhu Zhiyu Zhong Dr. Ying Ye Prof. Zixin Deng Prof. Yonghui Zhang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(24):9565-9571
While halogenated nucleosides are used as common anticancer and antiviral drugs, naturally occurring halogenated nucleosides are rare. Adechlorin (ade) is a 2′-chloro nucleoside natural product first identified from Actinomadura sp. ATCC 39365. However, the installation of chlorine in the ade biosynthetic pathway remains elusive. Reported herein is a Fe2+-α-ketoglutarate halogenase AdeV that can install a chlorine atom at the C2′ position of 2′-deoxyadenosine monophosphate to afford 2′-chloro-2′-deoxyadenosine monophosphate. Furthermore, 2′,3′-dideoxyadenosine-5′-monophosphate and 2′-deoxyinosine-5′-monophosphate can also be converted, albeit 20-fold and 2-fold, respectively, less efficiently relative to the conversion of 2′-deoxyadenosine monophosphate. AdeV represents the first example of a Fe2+-α-ketoglutarate-dependent halogenase that converts nucleotides into chlorinated analogues. 相似文献
997.
Dr. Christopher D. Fage Dr. Thomas Lathouwers Michiel Vanmeert Dr. Ling-Jie Gao Dr. Kristof Vrancken Eveline-Marie Lammens Angus N. M. Weir Ruben Degroote Prof. Harry Cuppens Dr. Simone Kosol Prof. Thomas J. Simpson Prof. Matthew P. Crump Prof. Christine L. Willis Prof. Piet Herdewijn Prof. Eveline Lescrinier Prof. Rob Lavigne Prof. Jozef Anné Dr. Joleen Masschelein 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(26):10636-10643
The enoyl-acyl carrier protein reductase enzyme FabI is essential for fatty acid biosynthesis in Staphylococcus aureus and represents a promising target for the development of novel, urgently needed anti-staphylococcal agents. Here, we elucidate the mode of action of the kalimantacin antibiotics, a novel class of FabI inhibitors with clinically-relevant activity against multidrug-resistant S. aureus. By combining X-ray crystallography with molecular dynamics simulations, in vitro kinetic studies and chemical derivatization experiments, we characterize the interaction between the antibiotics and their target, and we demonstrate that the kalimantacins bind in a unique conformation that differs significantly from the binding mode of other known FabI inhibitors. We also investigate mechanisms of acquired resistance in S. aureus and identify key residues in FabI that stabilize the binding of the antibiotics. Our findings provide intriguing insights into the mode of action of a novel class of FabI inhibitors that will inspire future anti-staphylococcal drug development. 相似文献
998.
A Far‐Red Fluorescent DNA Binder for Interaction Studies of Live Multidrug‐Resistant Pathogens and Host Cells 下载免费PDF全文
Harshavardhan Janga Prof. Dr. Bernd T. Schmeck Jun.‐Prof. Dr. Olalla Vázquez 《Angewandte Chemie (International ed. in English)》2018,57(36):11564-11568
Transgene expression of green fluorescent protein (GFP) has facilitated the spatiotemporal investigation of host–pathogen interactions; however, introduction of the GFP gene remains challenging in drug‐resistant bacteria. Herein, we report a novel far‐red fluorescent nucleic acid stain, 6‐TramTO‐3 , which efficiently labels bacteria through a DNA binding mode without affecting growth and viability. Exemplarily, we stained Klebsiella pneumoniae, a major threat to hospitalized patients, and deciphered divergent interaction strategies of antibiotic‐resistant and antibiotic‐sensitive Klebsiella strains with immune cells. 6‐TramTO‐3 constitutes an off‐the‐shelf reagent for real‐time analysis of bacterial infection, including strains for which the use of genetically encoded reporters is not feasible. Eventually, our approach may aid the development of strategies to combat a major worldwide health threat: multidrug‐resistant bacteria. 相似文献
999.
Dr. Shengyang Wang Prof. Jiansong Sun Qingju Zhang Dr. Xin Cao Yachen Zhao Prof. Gongli Tang Prof. Biao Yu 《Angewandte Chemie (International ed. in English)》2018,57(11):2884-2888
The proposed diastereoisomers ( 1 a – d ) together with their C8′‐epimers ( 1 e – h ) of amipurimycin, a unique antifungal peptidyl nucleoside antibiotic, have been synthesized for the first time. The synthetic approach is efficient and stereodivergent, and features a stereoselective aldol condensation to build the branched C9 sugar amino acid skeleton and a regio‐ and stereocontrolled gold(I)‐catalyzed N‐glycosylation to furnish the purine nucleoside. Analysis of the NMR data suggests that the previously assigned configuration of the tertiary C3′ in amipurimycin should be of opposite configuration. 相似文献
1000.
Pengxiao Fang Yanyun Bai Wanxu Wang Xiaoyuan Ma XiuMei Tai 《Journal of Dispersion Science and Technology》2018,39(7):1010-1017
To investigate the effect of content of polyether (F400) grafted on the properties of polysiloxane amphiphiles, polyether was grafted on the polysiloxane by hydrosilylation reaction with H2PtCl6 catalyst. The modified polysiloxanes were divided into two types; moreover, the ratio of polyether and polysiloxane was 1:1 or 1:2. The first one was similar to the conventional surfactant structure that is BA polysiloxane amphiphile, which own one hydrophobic chain and one hydrophilic group. Another one was ABA polysiloxane amphiphile, which possess one hydrophobic chain and two hydrophilic groups at the terminal. In our work, we compared the property of modified polysiloxanes with various contents of polyether in aqueous solution at room temperature to analyze the impact of polyether content on siloxane surfactants. The conclusion was that siloxane amphiphiles possess good solubility, high surface activity, and excellent spreading property. 相似文献