ChemBioChem最新文献_第7页

Conformational Constraint for Prevention of Aging of Organophosphate-Inhibited Acetylcholinesterase. 防止有机磷酸酯抑制乙酰胆碱酯酶衰老的构象约束。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-10 DOI: 10.1002/cbic.202500186

Francine S Katz, Ilya Trakht, Stevan Pecic, Alison Rinderspacher, Laura Schneider, Donald W Landry, Milan N Stojanovic

{"title":"Conformational Constraint for Prevention of Aging of Organophosphate-Inhibited Acetylcholinesterase.","authors":"Francine S Katz, Ilya Trakht, Stevan Pecic, Alison Rinderspacher, Laura Schneider, Donald W Landry, Milan N Stojanovic","doi":"10.1002/cbic.202500186","DOIUrl":"https://doi.org/10.1002/cbic.202500186","url":null,"abstract":"The covalent inhibition of acetylcholinesterase (AChE) by organophosphate compounds (OPCs) prevents the hydrolysis of the neurotransmitter, acetylcholine, and results in overstimulation of muscarinic and nicotinic receptors leading to severe cholinergic crisis. To treat toxic exposure to OPCs, the focus has been on using reactivator compounds (e.g., oximes) to reverse the adduct formation in the enzyme's active site, and to release the regenerated, active form of AChE. However, the interaction between the OPC inhibitor and the enzyme is usually followed by a secondary dealkylative reaction in which the OPC \"ages\", that is, produces an oxyanion on the phosphoryl group that cannot be recovered with standard reactivators. The unexpected discovey that immobilization of AChE prevented aging of OPC adducts led to the hypothesis that the inhibition and recovery pathways in AChE could be regulated by allosteric effectors that bind to the enzyme at a distance away from the site of inhibition. To demonstrate this, resistance to aging was replicated using bifunctional crosslinking of AChE in solution. This work provides the foundation to expand these principles to other potential effectors.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500186"},"PeriodicalIF":2.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Ligase-Based Two-Step Approach for the Generation of Bicyclic Peptides Containing a Benzylphenyl Thioether Framework. 一种基于连接酶的两步法生成含有苯苯基硫醚框架的双环肽。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-10 DOI: 10.1002/cbic.202500240

Hua Zhang, Hui-Min Wei, Jun-Hao Xue, Zhe-Min Xia, Feng-Hao Zheng, Xiao-Cui Wan, Li Zhou, Ge-Min Fang

引用次数: 0

Efficient Synthesis of Cleavable Cell-Penetrating Peptide-Cargo Conjugate via Low-Equivalent of Cell-Penetrating Peptide Activated by 2,2'-Dithiodipyridine. 利用2,2'-二硫代二吡啶活化的低当量CPP高效合成可切割CPP-货物偶联物。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-09 DOI: 10.1002/cbic.202500032

Pincheng Li, Xiaona Han, Beichen Wang, Yanyan Guo, Yu Wang, Yi-Ming Li

引用次数: 0

An Indole Dearomatization Strategy for the Synthesis of Pseudo-Natural Products. 假天然产物合成中的吲哚脱芳化策略。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-09 DOI: 10.1002/cbic.202500182

Joseph G F Hoock, Annina Burhop, Luca C Greiner, Beate Schölermann, Celine Da Cruz Lopes Guita, Jie Liu, Sukdev Bag, Axel Pahl, Sonja Sievers, Rebecca Scheel, Carsten Strohmann, Slava Ziegler, Michael Grigalunas, Herbert Waldmann

{"title":"An Indole Dearomatization Strategy for the Synthesis of Pseudo-Natural Products.","authors":"Joseph G F Hoock, Annina Burhop, Luca C Greiner, Beate Schölermann, Celine Da Cruz Lopes Guita, Jie Liu, Sukdev Bag, Axel Pahl, Sonja Sievers, Rebecca Scheel, Carsten Strohmann, Slava Ziegler, Michael Grigalunas, Herbert Waldmann","doi":"10.1002/cbic.202500182","DOIUrl":"10.1002/cbic.202500182","url":null,"abstract":"The indole moiety is a privileged fragment that frequently populates existing bioactive compound collections. The development of an indole-dearomatization sequence and its application for library expansion of a collection of indole-containing pseudo-natural products (NPs) are described. The resulting compounds are topologically distinct from the original compound class. Phenotyping by means of the cell painting assay initially indicates that the dearomatized compounds are morphologically different than the original pseudo-NP compound class and guiding NPs. However, analysis by means of a new subprofile analysis of the same cell painting assay data indicates that similar morphologies persist throughout the compound classes. Further biological studies support the findings of the subprofile analysis and highlight its potential to more effectively characterize novel compounds. The biological findings suggest that a plethora of indole-dearomatization reactions can be applied to existing indole-containing compound collections to rapidly access new biologically relevant scaffolds.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500182"},"PeriodicalIF":2.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thermal Folding of Peptides into Single α-Helical Turns. 肽热折叠成单个α-螺旋匝。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-08 DOI: 10.1002/cbic.202500050

Ankur Kumar, Erode N Prabhakaran

引用次数: 0

Biochemical Characterization of Multimodular Xylanolytic Carbohydrate Esterases from the Marine Bacterium Flavimarina sp. Hel_I_48. 海洋细菌Flavimarina sp.多模块木聚糖水解碳水化合物酯酶的生化特性

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-08 DOI: 10.1002/cbic.202500058

Michelle Teune, Thorben Döhler, Daniel Bartosik, Thomas Schweder, Uwe T Bornscheuer

{"title":"Biochemical Characterization of Multimodular Xylanolytic Carbohydrate Esterases from the Marine Bacterium Flavimarina sp. Hel_I_48.","authors":"Michelle Teune, Thorben Döhler, Daniel Bartosik, Thomas Schweder, Uwe T Bornscheuer","doi":"10.1002/cbic.202500058","DOIUrl":"https://doi.org/10.1002/cbic.202500058","url":null,"abstract":"Carbohydrate-active enzymes (CAZymes) are critical for sustainable biomass utilization due to their ability to degrade complex polysaccharides. Frequently, a multimodularity can be observed combining several CAZyme domains and activities in close proximity which can benefit this degradation process. In this study, three multimodular xylanolytic carbohydrate esterases (CEs), named Fl6, Fll1, and Fll4, originating from Flavimarina sp. Hel_I_48 that represent a novel arrangement of catalytic and/or binding domains, are investigated. While Fl6 acts as a glucuronyl esterase, it also contains a carbohydrate binding module which is normally associated with xylanase activity. Fll1 combines xylosidase with acetylxylan esterase (AXE) activity mediated by a CE3 domain. The third enzyme, Fll4, is the first enzyme that comprises three distinct CE domains and shows bifunctional activity as an AXE and a feruloyl esterase (FAE). Investigation of the single domains reveals that the CE6 domain of Fll4 mediates its AXE activity while one of the putative CE1 domains, CE1a, mediates the FAE activity. This investigation of multimodularity of marine CAZymes not only enhances our understanding of these enzymes but may provide a promising route toward more efficient algal biomass utilization for biotechnological applications.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500058"},"PeriodicalIF":2.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling. 泛素信号连锁类型特异性分析的分子工具箱。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-07 DOI: 10.1002/cbic.202500114

Julian Koch, Camilla Reiter Elbæk, Dominik Priesmann, Rune Busk Damgaard

{"title":"The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling.","authors":"Julian Koch, Camilla Reiter Elbæk, Dominik Priesmann, Rune Busk Damgaard","doi":"10.1002/cbic.202500114","DOIUrl":"10.1002/cbic.202500114","url":null,"abstract":"Modification of proteins and other biomolecules with ubiquitin regulates virtually all aspects of eukaryotic cell biology. Ubiquitin can be attached to substrates as a monomer or as an array of polyubiquitin chains with defined linkages between the ubiquitin moieties. Each ubiquitin linkage type adopts a distinct structure, enabling the individual linkage types to mediate specific functions or outcomes in the cell. The dynamics, heterogeneity, and in some cases low abundance, make analysis of linkage type-specific ubiquitin signaling a challenging and complex task. Herein, the strategies and molecular tools available for enrichment, detection, and characterization of linkage type-specific ubiquitin signaling, are reviewed. The molecular \"toolbox\" consists of a range of molecularly different affinity reagents, including antibodies and antibody-like molecules, affimers, engineered ubiquitin-binding domains, catalytically inactive deubiquitinases, and macrocyclic peptides, each with their unique characteristics and binding modes. The molecular engineering of these ubiquitin-binding molecules makes them useful tools and reagents that can be coupled to a range of analytical methods, such as immunoblotting, fluorescence microscopy, mass spectrometry-based proteomics, or enzymatic analyses to aid in deciphering the ever-expanding complexity of ubiquitin modifications.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500114"},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Persistent Myth of Limonene's Smell. 柠檬烯气味的持久神话。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-07 DOI: 10.1002/cbic.202401085

Klaus Roth, Hans Bauer, Birte J Sjursnes, Lise Kvittingen, Rudolf Schmid

引用次数: 0

Synthesis and Structure of Naphthoyl Thiourea-Based Binuclear Ruthenium(II) Arene Complexes: Studies on Anticancer Activity and Apoptotic Mechanism. 萘基硫脲基双核钌（II）芳烃配合物的合成与结构：抗癌活性及凋亡机制研究。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-07 DOI: 10.1002/cbic.202500057

Abirami Arunachalam, Ramesh Rengan

{"title":"Synthesis and Structure of Naphthoyl Thiourea-Based Binuclear Ruthenium(II) Arene Complexes: Studies on Anticancer Activity and Apoptotic Mechanism.","authors":"Abirami Arunachalam, Ramesh Rengan","doi":"10.1002/cbic.202500057","DOIUrl":"10.1002/cbic.202500057","url":null,"abstract":"Herein, the synthesis, characterization, and anticancer activity of ruthenium(II) p-cymene complexes comprising naphthoyl thiourea-based ligands are described. The synthesized N^O and N^S chelating ruthenium(II) complexes (1-3) are fully characterized by elemental analysis and spectral (fourier transform-infrared, Ultraviolet-visible, nuclear magnetic resonance, mass) methods. The structure of complex 2 has been elucidated by employing single-crystal X-ray diffraction, which verifies the two bidentate N^O and N^S coordination of the thiourea ligand to two Ru(II) centers. All the complexes have been screened for their anticancer efficacy in breast (MCF-7), colon (HT-29), liver (HepG2) cancerous cells, and noncancerous kidney (Hek-293) cells. Among them, complex 2 with an IC50 concentration of 3.59 ± 0.72 μm exhibits the most potent activity in HT-29 cells, surpassing the positive control, cisplatin. This may be due to the hydrophobic nature of the p-cymene moiety and electron-releasing methoxy group in the ligand scaffold. In addition, acridine orange-ethidium bromide and Hoechst labeling of all the complexes (1-3) on HT-29 cells reveal morphological alterations such as nuclear fragmentation and chromatin condensation resulting from the death of cancerous cells via apoptosis. Biochemical assays such as reactive oxygen species, mitochondrial membrane potential, and flow cytometry strongly confirm the cell death via mitochondrial dysfunction-mediated apoptosis.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500057"},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of Surfactin Biosynthesis in Bacillus Subtilis Using Cell-Permeable Adenylation Domain Inhibitors. 细胞渗透性腺苷化结构域抑制剂抑制枯草芽孢杆菌表面素合成的研究。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-07 DOI: 10.1002/cbic.202500136

Fumihiro Ishikawa, Sho Konno, Hideaki Kakeya, Genzoh Tanabe

{"title":"Inhibition of Surfactin Biosynthesis in Bacillus Subtilis Using Cell-Permeable Adenylation Domain Inhibitors.","authors":"Fumihiro Ishikawa, Sho Konno, Hideaki Kakeya, Genzoh Tanabe","doi":"10.1002/cbic.202500136","DOIUrl":"10.1002/cbic.202500136","url":null,"abstract":"Several natural bacterial virulence factors are biosynthesized by nonribosomal peptide synthetases (NRPSs). Therefore, NRPSs producing such natural products have emerged as attractive antibiotic targets. N-(aminoacyl)sulfamoyladenosine (aminoacyl-AMS) derivatives with chemical modifications at 2'-OH group of the adenosine skeleton are previously reported that inhibit NRPS amino acid adenylation (A) domains in recombinant enzyme systems, cellular lysates, and bacterial cells. The introduction of a couple of functionalities at the 2'-OH group preserves the binding affinity toward NRPS amino acid A-domains and improves cell permeability of the AMS scaffold. However, the effects of these compounds on secondary metabolism have not yet been explored. In this study, an affinity-based protein profiling (AfBPP) probe, L-Leu-AMS-BPyne, is validated for in-cell applications, including imaging of NRPS activities in bacteria. Next, L-Leu-AMS derivatives incorporating methyl, benzyl, and cyanomethyl functionalities at the 2'-OH group are synthesized and their inhibitory activity toward intracellular surfactin-NRPSs in the surfactin-producer Bacillus subtilis ATCC 21332 are investigated using the AfBPP probe. Finally, the attenuation of surfactin production using a Leu-AMS-BPyne probe and L-Leu-AMS derivatives in B. subtilis is demonstrated. These results indicate that chemical modifications at the 2'-OH group provide a way to develop cell-permeable and functional NRPS A-domain inhibitors.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500136"},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0