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111.
Dr. Camila M. Crnkovic Dr. Jana Braesel Dr. Aleksej Krunic Prof. Dr. Alessandra S. Eustáquio Prof. Dr. Jimmy Orjala 《Chembiochem : a European journal of chemical biology》2020,21(6):845-852
Cyanobactins are a large family of cyanobacterial ribosomally synthesized and post-translationally modified peptides (RiPPs) often associated with biological activities, such as cytotoxicity, antiviral, and antimalarial activities. They are traditionally described as cyclic molecules containing heterocyclized amino acids. However, this definition has been recently challenged by the discovery of short, linear cyanobactins containing three to five amino acids as well as cyanobactins containing no heterocyclized residues. Herein we report the discovery of scytodecamide ( 1 ) from the freshwater cyanobacterium Scytonema sp. UIC 10036. Structural elucidation based on mass spectrometry, 1D and 2D NMR spectroscopy, and Marfey's method revealed 1 to be a linear decapeptide with an N-terminal N-methylation and a C-terminal amidation. The genome of Scytonema sp. UIC 10036 was sequenced, and bioinformatic analysis revealed a cyanobactin-like biosynthetic gene cluster consistent with the structure of 1 . The discovery of 1 as a novel linear peptide containing an N-terminal N-methylation and a C-terminal amidation expands the chemical and genetic diversity of the cyanobactin family of compounds. 相似文献
112.
Jan Rinkel Prof. Dr. Jeroen S. Dickschat 《Chembiochem : a European journal of chemical biology》2020,21(6):807-810
Isotopic labeling experiments performed with a newly identified bacterial trichoacorenol synthase established a 1,5-hydride shift occurring in the cyclization mechanism. During EI-MS analysis, major fragments of the sesquiterpenoid were shown to arise via cryptic hydrogen movements. Therefore, the interpretation of earlier results regarding the cyclization mechanism obtained by feeding experiments in Trichoderma is revised. 相似文献
113.
Dr. Michael Stadlmeier Leander Simon Runtsch Filipp Streshnev Prof. Dr. Martin Wühr Prof. Dr. Thomas Carell 《Chembiochem : a European journal of chemical biology》2020,21(1-2):103-107
Mass spectrometry is the method of choice for the characterisation of proteomes. Most proteins operate in protein complexes, in which their close association modulates their function. However, with standard MS analysis, information on protein–protein interactions is lost and no structural information is retained. To gain structural and interactome data, new crosslinking reagents are needed that freeze inter- and intramolecular interactions. Herein, the development of a new reagent, which has several features that enable highly sensitive crosslinking MS, is reported. The reagent enables enrichment of crosslinked peptides from the majority of background peptides to facilitate efficient detection of low-abundant crosslinked peptides. Due to the special cleavable properties, the reagent can be used for MS2 and potentially for MS3 experiments. Thus, the new crosslinking reagent, in combination with high-end MS, should enable sensitive analysis of interactomes, which will help researchers to obtain important insights into cellular states in health and diseases. 相似文献
114.
Dr. Elena S. Reckzeh Prof. Dr. Dr. Herbert Waldmann 《Chembiochem : a European journal of chemical biology》2020,21(1-2):45-52
Glucose addiction is observed in cancer and other diseases that are associated with hyperproliferation. The development of compounds that restrict glucose supply and decrease glycolysis has great potential for the development of new therapeutic approaches. Addressing facilitative glucose transporters (GLUTs), which are often upregulated in glucose-dependent cells, is therefore of particular interest. This article reviews a selection of potent, isoform-selective GLUT inhibitors and their biological characterization. Potential therapeutic applications of GLUT inhibitors in oncology and other diseases that are linked to glucose addiction are discussed. 相似文献
115.
Carina A. Sommer Dr. Andreas Eichinger Prof. Dr. Arne Skerra 《Chembiochem : a European journal of chemical biology》2020,21(4):469-472
Boronic acids have long been known to form cyclic diesters with cis-diol compounds, including many carbohydrates. This phenomenon was previously exploited to create an artificial lectin by incorporating p-borono-l -phenylalanine (Bpa) into the ligand pocket of an engineered lipocalin, resulting in a so-called Borocalin. Here we describe the X-ray analysis of its covalent complex with 4-nitrocatechol as a high-affinity model ligand. As expected, the crystal structure reveals the formation of a cyclic diester between the biosynthetic boronate side chain and the two ortho-hydroxy substituents of the benzene ring. Interestingly, the boron also has a hydroxide ion associated, despite an only moderately basic pH 8.5 in the crystallization buffer. The complex is stabilized by a polar contact to the side chain of Asn134 within the ligand pocket, thus validating the functional design of the Borocalin as an artificial sugar-binding protein. Our structural analysis demonstrates how a boronate can form a thermodynamically stable diester with a vicinal diol in a tetrahedral configuration in aqueous solution near physiological pH. Moreover, our data provide a basis for the further engineering of the Borocalin with the goal of specific recognition of biologically relevant glycans. 相似文献
116.
Eva-Maria Herrlinger Mirjam Hau Dr. Desiree Melanie Redhaber Dr. Gabriele Greve Dr. Dominica Willmann Simon Steimle Prof. Dr. Michael Müller Prof. Michael Lübbert Dr. Christoph Cornelius Miething Prof. Roland Schüle Prof. Manfred Jung 《Chembiochem : a European journal of chemical biology》2020,21(16):2329-2347
Lysine-specific demethylase 1 (LSD1) has evolved as a promising therapeutic target for cancer treatment, especially in acute myeloid leukaemia (AML). To approach the challenge of site-specific LSD1 inhibition, we developed an enzyme-prodrug system with the bacterial nitroreductase NfsB (NTR) that was expressed in the virally transfected AML cell line THP1-NTR+. The cellular activity of the NTR was proven with a new luminescent NTR probe. We synthesised a diverse set of nitroaromatic prodrugs that by design do not affect LSD1 and are reduced by the NTR to release an active LSD1 inhibitor. The emerging side products were differentially analysed using negative controls, thereby revealing cytotoxic effects. The 2-nitroimidazolyl prodrug of a potent LSD1 inhibitor emerged as one of the best prodrug candidates with a pronounced selectivity window between wild-type and transfected THP1 cells. Our prodrugs are selectively activated and release the LSD1 inhibitor locally, proving their suitability for future targeting approaches. 相似文献
117.
Robert M. Samples Prof. Dr. Marcy J. Balunas 《Chembiochem : a European journal of chemical biology》2020,21(19):2708-2721
Probing the composition of the microbiome and its association with health and disease states is more accessible than ever due to the rise of affordable sequencing technology. Despite advances in our ability to identify members of symbiont communities, untangling the chemical signaling that they use to communicate with host organisms remains challenging. In order to gain a greater mechanistic understanding of how the microbiome impacts health, and how chemical ecology can be leveraged to advance small-molecule drug discovery from microorganisms, the principals governing communication between host and symbiont must be elucidated. Herein, we review common modes of interkingdom small-molecule communication in terrestrial and marine environments, describe the differences between these environments, and detail the advantages and disadvantages for studies focused on the marine environment. Finally, we propose the use of plant-endophyte interactions as a stepping stone to a greater understanding of similar interactions in marine invertebrates, and ultimately in humans. 相似文献
118.
Ming Hu Qinyu Han Prof. Dr. Bengang Xing 《Chembiochem : a European journal of chemical biology》2020,21(17):2512-2517
γ-Hydroxybutyric acid (GHB) functions as a depressant on the central nerve system and serves as a pharmaceutical agent in the treatment of narcolepsy and alcohol withdraw. In recent years, GHB has been misused as a recreational drug due to its ability to induce euphoric feelings. Moreover, it has gained increasing attention as a popular drug of abuse that is frequently related to drug-facilitated sexual assaults. At the moment, detection methods based on chromatography exhibit extraordinary sensitivity for GHB sensing. However, such techniques require complicated sample treatment prior to analysis. Optical sensors provide an alternative approach for rapid and simple analysis of GHB samples. Unfortunately, currently reported probes are mostly based on hydrogen bonding to recognize GHB, and this raises concerns about, for example, the lack of specificity. In this work, we report a bioinspired strategy for selective sensing of GHB. The method is based on specific enzyme recognition to allow highly selective detection of GHB with minimum interference, even in a complex sample matrix (e. g., simulated urine). In addition, the result can be obtained by either quantitative spectroscopy analysis or colorimetric change observed by the naked-eye, thus demonstrating its potential application in drug screening and forensic analysis. 相似文献
119.
Dr. Yu-ki Tanaka Risako Iida Shohei Takada Tetsuo Kubota Michiko Yamanaka Naoki Sugiyama Dr. Yolande Abdelnour Prof. Yasumitsu Ogra 《Chembiochem : a European journal of chemical biology》2020,21(22):3266-3272
The elemental composition of a single yeast, green alga, or red blood cell (RBC) was precisely determined by using inductively coupled plasma-mass spectrometry (ICP-MS) operating in fast time-resolved analysis (TRA) mode. The technique is known as single-cell (SC)-ICP-MS. Phosphorus, sulfur, magnesium, zinc, and iron were detected in the three types of cell. The elemental composition of yeast and green alga obtained by SC-ICP-MS was consistent with results obtained from conventional ICP-MS measurements following acid digestion of the cells. Slight differences were found in the measured values between SC-ICP-MS and the conventional ICP-MS results for RBC. However, the SC-ICP-MS results for S and Fe in RBC were closer to the estimated values for these elements that were calculated from the level of hemoglobin in RBCs. The data suggest that SC-ICP-MS is suitable for the analysis of various cell types, namely, fungus, plant, and animal cells. 相似文献
120.
Prof. C. Menor Salván Dr. Marcos Bouza Dr. David M. Fialho Dr. Bradley T. Burcar Prof. Facundo M. Fernández Prof. Nicholas V. Hud 《Chembiochem : a European journal of chemical biology》2020,21(24):3504-3510
Urea appears to be a key intermediate of important prebiotic synthetic pathways. Concentrated pools of urea likely existed on the surface of the early Earth, as urea is synthesized in significant quantities from hydrogen cyanide or cyanamide (widely accepted prebiotic molecules), it has extremely high water solubility, and it can concentrate to form eutectics from aqueous solutions. We propose a model for the origin of a variety of canonical and non-canonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs.The dual nucleophilic-electrophilic character of urea makes it an ideal precursor for the formation of nitrogenous heterocycles. We propose a model for the origin of a variety of canonical and noncanonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs. These reactions involve urea condensation with other prebiotic molecules (e. g., malonic acid) that could be driven by environmental cycles (e. g., freezing/thawing, drying/wetting). The resulting heterocycle assemblies are compatible with the formation of nucleosides and, possibly, the chemical evolution of molecular precursors to RNA. We show that urea eutectics at moderate temperature represent a robust prebiotic source of nitrogenous heterocycles. The simplicity of these pathways, and their independence from specific or rare geological events, support the idea of urea being of fundamental importance to the prebiotic chemistry that gave rise to life on Earth. 相似文献