ChemBioChem最新文献_第6页

A Perspective on Covalent Hit Identification and Validation in the European Pharmaceutical Industry 欧洲制药工业共价命中鉴定和验证的展望

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-31 DOI: 10.1002/cbic.70523

Oliver Schadt, Sebastian Essig, Giambattista Testolin

引用次数: 0

A Co-Chaperone Mimetic Perturbs Cellular Nitrogen Metabolism in Mycobacteria 一种协同伴侣模拟物扰乱了分枝杆菌的细胞氮代谢

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-31 DOI: 10.1002/cbic.70504

Brock Nelson, Tania J. Lupoli

{"title":"A Co-Chaperone Mimetic Perturbs Cellular Nitrogen Metabolism in Mycobacteria","authors":"Brock Nelson, Tania J. Lupoli","doi":"10.1002/cbic.70504","DOIUrl":"https://doi.org/10.1002/cbic.70504","url":null,"abstract":"Protein quality control in bacteria relies on dynamic chaperone networks that rapidly respond to environmental stresses. In mycobacteria, a central Hsp70 chaperone, DnaK, and its co-chaperones, J-domain proteins (JDPs), play essential roles in the cellular response to stress and antibiotics. Conserved “J-domain” sequences of JDPs are known to mediate transient interactions with Hsp70s and other protein partners. We have previously shown that a rationally designed proteomimetic of a J-domain is toxic to stressed mycobacterial cells. Here, we aimed to trap J-domain mimetic interaction partners to potentially reveal vulnerabilities in cellular stress-response pathways. To do so, we modified a J-domain proteomimetic of the mycobacterial JDP DnaJ1 (J1C) with a photoaffinity label moiety, resulting in J1C–PAL. In heat-shocked mycobacteria, J1C–PAL crosslinked to DnaK in cells, confirming retention of canonical Hsp70-binding activity under proteotoxic stress. Chemoproteomic profiling revealed additional cellular targets, namely a conditionally essential mycobacterial protein, glutamine synthetase (GS). Biochemical assays demonstrated that J1C–PAL bound GS and inhibited its enzymatic activity. Cellular studies validated that J1C perturbed nitrogen metabolism mediated by GS in mycobacteria. Together, these findings establish J1C–PAL as a cell-permeable chemoproteomic tool for mapping protein targets and uncover a surprising link between a co-chaperone mimetic and bacterial metabolism.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860057","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

Synergistic Action of Rhizopus oryzae Lipase and Fusarium oxysporum Cutinase in the Enzymatic Transesterification of a High-Free Fatty Acid Oil 米根霉脂肪酶和尖孢镰刀菌角质酶在高游离脂肪酸油酶交换中的协同作用

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-31 DOI: 10.1002/cbic.70506

Androniki Spanou, Eirini Manoura, Ioannis Spanakis, Ioannis V. Pavlidis

{"title":"Synergistic Action of Rhizopus oryzae Lipase and Fusarium oxysporum Cutinase in the Enzymatic Transesterification of a High-Free Fatty Acid Oil","authors":"Androniki Spanou, Eirini Manoura, Ioannis Spanakis, Ioannis V. Pavlidis","doi":"10.1002/cbic.70506","DOIUrl":"https://doi.org/10.1002/cbic.70506","url":null,"abstract":"High-free fatty acid oil cannot be converted to biodiesel through conventional chemical processes and accumulates as a waste stream in biodiesel industries. In this work, a bienzymatic system comprising Rhizopus oryzae lipase (ROL) and Fusarium oxysporum cutinase (FOC) was developed for its transesterification. Preliminary experiments, followed by response surface methodology, identified the optimal conditions of ROL/FOC ratio of 3.9:1 (mg/mg), a methanol-to-oil molar ratio of 2.6:1 applied through three stepwise additions, and a temperature of 31.8 °C, yielding a maximum conversion of 69.6% after 48 h. Under these conditions, FOC alone led only to ~4% conversion, while the combined ROL/FOC system outperformed ROL alone by approximately 18% after 72 h, demonstrating a potential synergistic effect between the two enzymes. To enhance process sustainability, FOC was immobilized on four carriers, with macroporous divinylbenzene and amino C6 methacrylate to perform the best, enabling the reuse over three consecutive cycles with minimal activity loss and achieving conversions up to 91% after 72 h in the second use. High efficiency was maintained upon scale-up to 100 mL, demonstrating process robustness. The synergistic action of ROL and FOC provides an effective biocatalytic route for the valorization of low-value, free fatty acid-rich lipid feedstocks into biodiesel.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sustainable Biocatalytic Cascades: A Versatile Tool in the Synthesis of Natural Products With Therapeutic Potential 可持续生物催化级联：具有治疗潜力的天然产物合成的多功能工具

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-31 DOI: 10.1002/cbic.70492

Ram N. Yadav, Sovan Dey, Satyendra Kumar Pandey, Anup Barman, Md. Firoj Hossain, Luciana C. Schmidt, Vandana Singh

{"title":"Sustainable Biocatalytic Cascades: A Versatile Tool in the Synthesis of Natural Products With Therapeutic Potential","authors":"Ram N. Yadav, Sovan Dey, Satyendra Kumar Pandey, Anup Barman, Md. Firoj Hossain, Luciana C. Schmidt, Vandana Singh","doi":"10.1002/cbic.70492","DOIUrl":"https://doi.org/10.1002/cbic.70492","url":null,"abstract":"Biocascade catalysis has emerged as a defining paradigm in contemporary synthesis, enabling the orchestration of multiple enzymatic transformations within a single vessel. By allowing intermediates to flow seamlessly between successive steps without isolation, cascades emulate the elegance of natural biosynthetic networks while delivering significant gains in atom economy and operational simplicity. The intrinsic chemo-, regio-, and stereoselectivity of enzymes facilitates the construction of architecturally complex, enantiomerically enriched molecules under mild, aqueous, and environmentally benign conditions. In this way, biocascade strategies accelerate the generation of molecular diversity while embodying the principles of sustainable chemistry by reducing energy demand, solvent use, and waste generation. Recent advances in protein engineering, directed evolution, computational enzyme design, and synthetic biology have expanded the scope of enzymatic cascades, transforming nature's catalytic repertoire into scalable synthetic technologies. Landmark studies now demonstrate their transformative potential in the assembly of complex polyketides, bioactive alkaloids, pharmaceuticals, and active pharmaceutical ingredients (APIs), as well as diverse heterocyclic scaffolds of medicinal relevance. Collectively, these achievements underscore the growing significance of biocascade catalysis as a cornerstone of modern synthesis, bridging the ingenuity of biological systems with the imperatives of next-generation drug discovery and sustainable chemical manufacturing.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860054","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

Benzylamine-Based Organoselenium Compounds as Glutathione Peroxidase Mimics: Antioxidant and Antibacterial Agents 以苄胺为基础的有机硒化合物作为谷胱甘肽过氧化物酶模拟物：抗氧化剂和抗菌剂

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-31 DOI: 10.1002/cbic.70510

Nikhil Sodhi, Rajni Kadian, Aboobacker P. A., Thiyagarajan Sanjeevi, Vijay P. Singh

引用次数: 0

Peptide Aptamers: Innovative Design and Applications in Pathogen Detection 肽适体：创新设计及其在病原体检测中的应用

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-31 DOI: 10.1002/cbic.70525

Shengjie Wu, Xiaoyu Wu, Jie Wen, Junwen Chen, Tonggong Liu, Dayong Gu

{"title":"Peptide Aptamers: Innovative Design and Applications in Pathogen Detection","authors":"Shengjie Wu, Xiaoyu Wu, Jie Wen, Junwen Chen, Tonggong Liu, Dayong Gu","doi":"10.1002/cbic.70525","DOIUrl":"https://doi.org/10.1002/cbic.70525","url":null,"abstract":"Peptide aptamers are short synthetic peptides that recognize targets with high affinity and specificity, offering advantages over antibodies and nucleic acid aptamers in size, structural flexibility, biocompatibility, and ease of chemical modification. Their design has progressed from traditional experimental screening to advanced computational approaches, such as structure-based rational design and artificial intelligence-driven generation. These methods have substantially enhanced screening efficiency and binding performance. For pathogen detection, biosensors employing peptide aptamers enable the rapid, sensitive, and specific identification of viruses, parasites, and other pathogens. Although challenges in affinity and stability remain, ongoing innovation positions peptide aptamers as a promising molecular tool for next-generation diagnostic platforms. This review systematically summarizes the design and key technological advances in peptide aptamers, emphasizing both traditional experimental screening and computer-aided design strategies. It also highlights representative applications of peptide aptamers in pathogen detection, providing a reference for developing high-performance recognition elements and novel detection platforms.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860055","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

Sanger’s Reagent-Mediated Prodrug for Light-Controlled Release of Camptothecin With Fluorescent Indication Sanger试剂介导的喜树碱光控释放前药具有荧光适应症。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-27 DOI: 10.1002/cbic.70502

Zhennan Jiang, Gengwen Chen, Ming Liu, Fang Wang, Sheng Lu, Xiaoqiang Chen

{"title":"Sanger’s Reagent-Mediated Prodrug for Light-Controlled Release of Camptothecin With Fluorescent Indication","authors":"Zhennan Jiang, Gengwen Chen, Ming Liu, Fang Wang, Sheng Lu, Xiaoqiang Chen","doi":"10.1002/cbic.70502","DOIUrl":"10.1002/cbic.70502","url":null,"abstract":"Stimuli-responsive prodrug system has emerged as an attractive approach to address the issues encountered by conventional chemotherapeutics. Among the growing arsenal of stimuli-responsive prodrug strategies, the photocaging approach occupies a privileged position because it replaces poorly controlled biological triggers with an external light stimulation, thereby offering a promising solution to the therapeutic limitations in cancer treatment. In this work, we have developed a Sanger’s reagent based prodrug, Sanger-Naph-CPT, which enables light-controlled camptothecin (CPT) release in cancer cells via 400 nm light. Integrating a naphthalimide fluorescent reporter, the system allows real-time monitoring of drug release kinetics. The photocaged prodrug was characterized by HPLC/HRMS, confirming photodegradation under light. Confocal microscopy showed minimal baseline fluorescence in HeLa cells without irradiation, with robust fluorescence emerging postirradiation (intensity increasing with exposure time). MTT assays showed that, after light irradiation, Sanger-Naph-CPT exhibited dose-dependent cytotoxicity comparable to free CPT, demonstrating restored activity of released CPT. This dual-function platform combines light-triggered therapeutic activity and fluorescence reporting, offering a modular design for photocontrolled prodrugs.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 16","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838680","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

Development of a Photostable pH Biosensor Based on mStayGold 基于mStayGold的光稳定pH生物传感器的研制。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-26 DOI: 10.1002/cbic.70512

Michael Chang, Lilly Nash, Ruben Bierings, Kei Takahashi-Yamashiro, Takuya Terai, Tom Carter, Robert E. Campbell, Kelvin K. Tsao

{"title":"Development of a Photostable pH Biosensor Based on mStayGold","authors":"Michael Chang, Lilly Nash, Ruben Bierings, Kei Takahashi-Yamashiro, Takuya Terai, Tom Carter, Robert E. Campbell, Kelvin K. Tsao","doi":"10.1002/cbic.70512","DOIUrl":"10.1002/cbic.70512","url":null,"abstract":"Fluorescent proteins (FPs) that are pH-sensitive play a crucial role in investigating pH-related cellular processes, such as endocytosis and exocytosis. Existing pH-sensitive FPs generated from Aequorea victoria green fluorescent protein (GFP), such as superecliptic pHluorin (SEP) and Lime, have been widely employed to study these processes, but suffer from low photostability. Here, we report the development and characteristics of serapH, a genetically encodable pH biosensor with improved photostability compared to GFP analogues, which we generated using mStayGold as a scaffold. To aid in the development of serapH, we developed a method for screening pH-sensitive FP variants by directly evaluating both brightness and pH sensitivity in bacterial colonies on agar. This significantly increased the number of colonies that could be screened per round and reduced the time needed per round. The photostability of serapH should improve spatiotemporal resolution by increasing tolerance to higher excitation intensities and longer imaging durations, thereby expanding the range of applications of pH-sensitive FPs.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 16","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13509110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Restoring Meropenem Activity Against VIM-1-Producing Klebsiella pneumoniae Through Zinc-Binding Ligands 通过锌结合配体恢复美罗培南对产vim -1肺炎克雷伯菌的活性

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-26 DOI: 10.1002/cbic.70509

Chiara Ragusa, Ruqaiya Khalil, Valentina Giglio, Kaveh Eskandari, Fraser J. Scott, Attilio V. Vargiu, Graziella Vecchio

{"title":"Restoring Meropenem Activity Against VIM-1-Producing Klebsiella pneumoniae Through Zinc-Binding Ligands","authors":"Chiara Ragusa, Ruqaiya Khalil, Valentina Giglio, Kaveh Eskandari, Fraser J. Scott, Attilio V. Vargiu, Graziella Vecchio","doi":"10.1002/cbic.70509","DOIUrl":"10.1002/cbic.70509","url":null,"abstract":"The growing prevalence of metallo-β-lactamase (MBL)-producing bacteria threatens the clinical efficacy of carbapenems such as meropenem. To investigate potential strategies for restoring β-lactam activity, a panel of compounds was evaluated as putative MBL inhibitors and antibiotic adjuvants. The panel included FDA-approved drugs (carbonic anhydrase inhibitors, an antiviral agent, and a metal chelator), and two novel histidine–pyridine derivatives (D- and L-2-amino-3-(1H-imidazol-4-yl)-N-[2-(pyridin-2-yl)ethyl]propenamides). The latter were synthesized and characterized by NMR spectroscopy and mass spectrometry. Combination assays against Verona Integron–encoded Metallo-β-Lactamase 1 (VIM-1)–producing Klebsiella pneumoniae showed that D-penicillamine and chlorpropamide restored meropenem activity. These effects were supported by time-dependent inhibition and checkerboard assays. Molecular docking and MD simulations with the VIM-1 enzyme further elucidated the putative binding modes of these inhibitors. These results suggest that repurposing the conventional D-penicillamine and chlorpropamide drugs can effectively counteract MBL-mediated resistance.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 16","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13509051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional Characterization of Conserved Positively Charged Residues Surrounding the Ligand-Binding Pocket in Plant Cryptochromes 植物隐色素配体结合袋周围保守带正电残基的功能表征。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-08-26 DOI: 10.1002/cbic.202500946

Mengqi Wan, Hao Liu, Jiaying Zhang, Xiaoyu Feng, Xin Guang, Shuchang Hu, Xiaoran Li, Min Wei, Wenxin Yin, Jun Lv, Bin Wen

{"title":"Functional Characterization of Conserved Positively Charged Residues Surrounding the Ligand-Binding Pocket in Plant Cryptochromes","authors":"Mengqi Wan, Hao Liu, Jiaying Zhang, Xiaoyu Feng, Xin Guang, Shuchang Hu, Xiaoran Li, Min Wei, Wenxin Yin, Jun Lv, Bin Wen","doi":"10.1002/cbic.202500946","DOIUrl":"10.1002/cbic.202500946","url":null,"abstract":"Plant cryptochromes are blue light-responsive photoreceptor proteins that regulate various photoresponses throughout plant growth and development. Compared with their homologous CPD I/III photolyases, plant cryptochromes have lost DNA repair activity but evolved signal transduction functions. The structurally conserved ligand-binding pocket, which corresponds to the photolyase active site, exhibits distinctive features in plant cryptochromes, with key binding residues being altered relative to photolyases. Notably, the distribution of charged amino acids around this pocket differs markedly between the two protein families. In this study, we identified two conserved positively charged residues (Arg237 and Arg357) flanking this pocket in Chlamydomonas reinhardtii cryptochrome (pCRY) and its Arabidopsis homologs. Biochemical and physiological analyses demonstrated that these residues effectively modulate photoreduction kinetics and oxidative stability of the flavin adenine dinucleotide (FAD) cofactor, participate in ATP binding, and ultimately influence flowering time in transgenic Arabidopsis plants. Our findings reveal that these conserved positively charged sites play critical roles in regulating the photosensitivity and functional stability of plant cryptochromes.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 16","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816876","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