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61.
Therese Planke Katarina Cirnski Dr. Jennifer Herrmann Prof. Dr. Rolf Müller Prof. Dr. Andreas Kirschning 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(19):4289-4296
Cystobactamids belong to the group of arene-based oligoamides that effectively inhibit bacterial type IIa topoisomerases. Cystobactamid 861-2 is the most active member of these antibiotics. Most amide bonds present in the cystobactamids link benzoic acids with anilines and it was found that some of these amide bonds undergo chemical and enzymatic hydrolysis, especially the one linking ring C with ring D. This work reports on the chemical synthesis and biological evaluation of thirteen new cystobactamids that still contain the methoxyaspartate hinge. However, we exchanged selected amide bonds either by the urea or the triazole groups and modified ring A in the latter case. While hydrolytic stability could be improved with these structural substitutes, the high antibacterial potency of cystobactamid 861-2 could only be preserved in selected cases. This includes derivatives, in which the urea group is positioned between rings A and B and where the triazole is found between rings C and D. 相似文献
62.
Dr. Dennis Kubiczek Heinz Raber Dr. Nicholas Bodenberger Thomas Oswald Melis Sahan Daniel Mayer Dr. Sebastian Wiese Prof. Dr. Steffen Stenger Prof. Dr. Tanja Weil Dr. Frank Rosenau 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(64):14536-14545
Textbook procedures require the use of individual aptamers enriched in SELEX libraries which are subsequently chemically synthesized after their biochemical characterization. Here we show that this reduction of the available sequence space of large libraries and thus the diversity of binding molecules reduces the labelling efficiency and fidelity of selected single aptamers towards different strains of the human pathogen Pseudomonas aeruginosa compared to a polyclonal aptamer library enriched by a whole-cell-SELEX involving fluorescent aptamers. The library outperformed single aptamers in reliable and specific targeting of different clinically relevant strains, allowed to inhibit virulence associated cellular functions and identification of bound cell surface targets by aptamer based affinity purification and mass spectrometry. The stunning ease of this FluCell-SELEX and the convincing performance of the P. aeruginosa specific library may pave the way towards generally new and efficient diagnostic techniques based on polyclonal aptamer libraries not only in clinical microbiology. 相似文献
63.
Min Zhou Yuxin Qian Jiayang Xie Wenjing Zhang Weinan Jiang Ximian Xiao Sheng Chen Chengzhi Dai Zihao Cong Zhemin Ji Ning Shao Longqiang Liu Yuequn Wu Runhui Liu 《Angewandte Chemie (International ed. in English)》2020,59(16):6412-6419
Peptides have important biological functions. However, their susceptibility to proteolysis limits their applications. We demonstrated here for the first time, that poly(2‐oxazoline) (POX) can work as a functional mimic of peptides. POX‐based glycine pseudopeptides, a host defense peptide mimic, had potent activities against methicillin‐resistant S. aureus, which causes formidable infections. The POX mimic showed potent activity against persisters that are highly resistant to antibiotics. S. aureus did not develop resistance to POX owning to the reactive oxygen species related antimicrobial mechanism. POX‐treated S. aureus is sensitive to common antibiotics, demonstrating no observable antimicrobial pressure or cross‐resistance in using antimicrobial POX. This study highlights POX as a new type of functional mimic of peptides and opens new avenues in designing and exploring peptide mimetics for biological functions and applications. 相似文献
64.
Chunhua Zhao Shan Yan Qin Li Hucheng Zhu Zhiyu Zhong Ying Ye Zixin Deng Yonghui Zhang 《Angewandte Chemie (International ed. in English)》2020,59(24):9478-9484
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
65.
Shanwen Zhang Chun Gui Mingwei Shao Pachaiyappan Saravana Kumar 《Natural product research》2020,34(11):1499-1504
AbstractTunicamycin E (1), featuring a methyl substitution at C-10′, was isolated from marine-derived Streptomyces xinghaiensis SCSIO S15077 originated from the South China Sea sediment together with six known compounds, tunicamycin B (2), tunicamycin X (3), tunicamycin A (4), streptovirudin D2 (5), tunicamycin C (6), and tunicamycin C3 (7). The structure of compound 1 was elucidated by detailed spectroscopic data analyses. All the compounds exhibited strong to moderate antibacterial activity against Gram-positive bacteria Bacillus thuringiensis BT01 and B. thuringiensis W102 with MIC values ranging from 0.008 to 2 μg/mL. Moreover, compounds 1–7 exhibited moderate antifungal activity against Candida albicans ATCC 96901 and C. albicans CMCC (F) 98001 with MIC values ranging from 2 to 32 μg/mL. This is the first report that tunicamycins exhibit antimicrobial activities against B. thuringiensis, C. albicans CMCC (F) 98001 and a fluconazole resistant strain C. albicans ATCC 96901. 相似文献
66.
The residues and abuse of antibiotics have seriously endangered ecological balance and human health; meanwhile, antibiotics determination is very difficult because of their low levels and multiple categories in complicated matrices. Appropriate sample pretreatment is usually imperative to enrich (ultra)trace antibiotics and eliminate matrix interference prior to chromatographic analysis. Dispersive liquid-liquid microextraction (DLLME) has become an ideal pretreatment technique owing to its simplicity, effectiveness, low-consumption, etc. In this work, an ultrasonic-assisted DLLME (UA-DLLME) was developed for the simultaneous extraction of seven sulfonamides (SAs) antibiotics in environmental water and seafood samples coupled with HPLC-DAD determination. Several parameters affecting UA-DLLME efficiency were systematically optimized, and consequently the SAs were separated and detected within 14.5 min. The obtained limits of detection (LODs) and limits of quantification (LOQs) ranged from 0.7–7.8 μg/L and 2.4–26.0 μg/L for three water samples (seawater, aquaculture wastewater and lake water) and two seafood samples (pomfrets and shrimps). High recoveries (80.0–116.0%) with low relative standard deviations (0.1–8.1%) were achieved for all the tested samples at three spiked levels. Notably, sulfadimethoxine was found at 24.49 μg/L in one seawater sample. The facile, robust and benign DLLME-HPLC method demonstrated promising perspectives for multiresidue analysis of antibiotics. 相似文献
67.
固相萃取液相色谱-质谱/质谱联用测定河水中大环内酯类抗生素 总被引:19,自引:4,他引:19
应用固相萃取(SPE)及LC—MS/MS技术,建立了水中痕量大环内酯类抗生素即红霉素、脱水红霉素、罗红霉素的分析方法,优化了固相萃取、液相色谱-质谱/质谱等相关条件。水样经HLB固相萃取柱富集净化,以多反应检测方式(MRM)对待测物进行定性和定量分析。3种抗生素在10-2000ng/L范围内具有良好的线性。其定量下限为5ng/L(S/N〉10)。加标纯水和实际水样的回收率在71%-111%之间,相对标准偏差(RSD)在3.7%-8.6%之间。该方法灵敏度高、选择性好、准确度高,适合实际水样中痕量大环内酯类药物的检测。使用该方法测得珠江广州河段某水样中红霉素、脱水红霉素和罗红霉素质量浓度分别为164、291和134ng/L。 相似文献
68.
69.
Dr. Andreas A. Bastian Dr. Maria Bastian Dr. Manuel Jäger Mark Loznik Dr. Eliza M. Warszawik Xintong Yang Dr. Nabil Tahiri Dr. Peter Fodran Prof. Dr. Martin D. Witte Anne Thoma Dr. Jens Köhler Prof. Dr. Adriaan J. Minnaard Prof. Dr. Andreas Herrmann 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(36):e202200883
The continuous emergence of antimicrobial resistance is causing a threat to patients infected by multidrug-resistant pathogens. In particular, the clinical use of aminoglycoside antibiotics, broad-spectrum antibacterials of last resort, is limited due to rising bacterial resistance. One of the major resistance mechanisms in Gram-positive and Gram-negative bacteria is phosphorylation of these amino sugars at the 3’-position by O-phosphotransferases [APH(3’)s]. Structural alteration of these antibiotics at the 3’-position would be an obvious strategy to tackle this resistance mechanism. However, the access to such derivatives requires cumbersome multi-step synthesis, which is not appealing for pharma industry in this low-return-on-investment market. To overcome this obstacle and combat bacterial resistance mediated by APH(3’)s, we introduce a novel regioselective modification of aminoglycosides in the 3’-position via palladium-catalyzed oxidation. To underline the effectiveness of our method for structural modification of aminoglycosides, we have developed two novel antibiotic candidates overcoming APH(3’)s-mediated resistance employing only four synthetic steps. 相似文献
70.
TurboFlow在线净化/液相色谱-串联质谱法快速测定动物源性食品中聚醚类抗生素的研究 总被引:2,自引:0,他引:2
建立了Turbo Flow在线净化/液相色谱-串联质谱法快速同时测定牛奶、鸡肉和鸡蛋中拉沙洛菌素、盐霉素、莫能菌素、甲基盐霉素、马杜霉素和尼日利亚菌素残留的方法。样品提取液经在线净化柱Cyclone-p净化,Thermo Scientific Hypersil-Gold C8(150 mm×2.1 mm,5μm)色谱柱分离,电喷雾正离子模式测定,整个分析过程仅13 min。方法在1~100μg/L范围内呈良好线性关系(r≥0.999),定量下限为1μg/kg,在动物源性食品中3个加标水平下的回收率为71.9%~109.0%,相对标准偏差为1.5%~14.9%。 相似文献