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Illuminating antifungal mode of action and resistance with fluorescent probes 荧光探针阐明抗真菌作用方式及耐药性
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-04-01 Epub Date: 2025-02-17 DOI: 10.1016/j.cbpa.2025.102570
Moriah Jospe-Kaufman, Micha Fridman
{"title":"Illuminating antifungal mode of action and resistance with fluorescent probes","authors":"Moriah Jospe-Kaufman,&nbsp;Micha Fridman","doi":"10.1016/j.cbpa.2025.102570","DOIUrl":"10.1016/j.cbpa.2025.102570","url":null,"abstract":"<div><div>The rise in fungal infections, driven by pathogens resistant to the limited scope of antifungal agents available, poses an increasing threat to global health and the economy. Addressing this challenge requires a thorough understanding of the mechanisms of antifungal agents and the development of advanced resistance diagnostic methods. This opinion manuscript highlights recent advancements in antifungal research, with a focus on chemical biology approaches, particularly the development of fluorescent probes derived from various antifungal agents. These probes reveal new aspects of antifungal activity and provide deeper insights into modes of action and resistance mechanisms. Live cell imaging of fungal pathogens labeled with these probes has uncovered novel strategies to enhance antifungal efficacy, understand virulence factors, and detect resistance. These unique small-molecule tools offer powerful new avenues for addressing the fungal infections crisis, harnessing chemical biology approaches to develop innovative solutions to the global challenges posed by fungi.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"85 ","pages":"Article 102570"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Recent advances in high-throughput screening methods for small molecule modulators in bacteria 细菌小分子调节剂高通量筛选方法研究进展
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-04-01 Epub Date: 2025-02-14 DOI: 10.1016/j.cbpa.2025.102571
Hannah G. Addis , Erin E. Carlson
{"title":"Recent advances in high-throughput screening methods for small molecule modulators in bacteria","authors":"Hannah G. Addis ,&nbsp;Erin E. Carlson","doi":"10.1016/j.cbpa.2025.102571","DOIUrl":"10.1016/j.cbpa.2025.102571","url":null,"abstract":"<div><div>Bacterial infections, especially those that are resistant to antibiotics, constitute an increasing threat to public health. Deeper understanding about the systems that govern resistant infections, followed by the design of new therapies is crucial to minimizing morbidity and mortality due to antibacterial resistance. To this end, the discovery of small molecules capable of modulating bacterial processes is an important goal. Herein, we summarize recent developments in high-throughput screening, including the use of <em>in vitro</em> biochemical assays, reporter fusion read-out methods, and live cell phenotypic assays in bacteria. We also highlight key advantages and disadvantages of each assay type, as well as exciting new innovations.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"85 ","pages":"Article 102571"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Bacterial peptidoglycan as a living polymer 细菌肽聚糖是一种活的聚合物。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-12-18 DOI: 10.1016/j.cbpa.2024.102562
Amr M. El-Araby, Jed F. Fisher, Shahriar Mobashery
{"title":"Bacterial peptidoglycan as a living polymer","authors":"Amr M. El-Araby,&nbsp;Jed F. Fisher,&nbsp;Shahriar Mobashery","doi":"10.1016/j.cbpa.2024.102562","DOIUrl":"10.1016/j.cbpa.2024.102562","url":null,"abstract":"<div><div>The peptidoglycan manifests as a multifaceted component of the bacterial cell wall. Throughout the lifecycle of the bacterium, the peptidoglycan is deconstructed, rebuilt, and remodeled for bacterial cell growth and replication. Degradation products of the peptidoglycan serve as precursors for cell-wall building blocks <em>via</em> recycling processes and as signaling molecules. Cell-wall recycling and <em>de novo</em> cell-wall synthesis converge biochemically at the cytoplasmic compartment. Peptidoglycan biochemistry is finely tuned to maintain the polymer's functions and is intimately connected to antibiotic-resistance mechanisms. Cell-wall-modifying enzymes present a unique opportunity for the discovery of antibiotics and antibiotic adjuvants. The unique chemical template of the peptidoglycan has been a target of numerous chemical biology approaches for investigating its functions and modulation. In this review, we highlight the current perspective on peptidoglycan research. We present recent efforts to understand the peptidoglycan as a functional component of antibiotic resistance, and as a target for antimicrobial therapy.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102562"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Developing photoactivated artificial enzymes for sustainable fuel production 开发用于可持续燃料生产的光激活人工酶。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-12-29 DOI: 10.1016/j.cbpa.2024.102553
Ashlee E. Wertz , Hannah S. Shafaat
{"title":"Developing photoactivated artificial enzymes for sustainable fuel production","authors":"Ashlee E. Wertz ,&nbsp;Hannah S. Shafaat","doi":"10.1016/j.cbpa.2024.102553","DOIUrl":"10.1016/j.cbpa.2024.102553","url":null,"abstract":"<div><div>Enzymes catalyze molecular reactions with remarkable efficiency and selectivity under mild conditions. Photoactivated enzymes make use of a light-absorbing chromophore to drive chemical transformations, ideally using sunlight as an energy source. The direct attachment of a chromophore to native enzymes is advantageous, as information on the underlying catalytic mechanisms can be obtained. Artificial enzyme development seeks to mimic natural enzymes to generate valuable products with high efficiency in a simplified, robust framework. Light-initiated artificial enzymatic catalysis combines these strategies and represents a promising avenue for sustainable generation of value-added products. Furthermore, while early systems often combined three components for catalysis-- the enzyme, a photosensitizer, and a sacrificial electron donor-- we describe an adaptation of this approach in which the chromophore is immobilized on the enzyme, removing the need for diffusional collision. The latter is advantageous as it provides deeper insight into the catalytic mechanism and facilitates further optimization of the designed construct. In this opinion, we highlight several examples of light-driven, artificial metalloenzymes, and suggest that ongoing and future efforts should leverage prior mechanistic studies on native enzymes as a foundation for strategic design of next-generation photoactivated protein-based catalysts.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102553"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Corrigendum to “Drug discovery targeting Nav1.8: Structural insights and therapeutic potential” [Curr Opin Chem Biol 83 (2024) 102538] 针对 Nav1.8 的药物发现：结构见解和治疗潜力》[Curr Opin Chem Biol 83 (2024) 102538] 更正
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-11-25 DOI: 10.1016/j.cbpa.2024.102546
Huan Wang , Jian Huang , Jie Zang , Xueqin Jin , Nieng Yan
{"title":"Corrigendum to “Drug discovery targeting Nav1.8: Structural insights and therapeutic potential” [Curr Opin Chem Biol 83 (2024) 102538]","authors":"Huan Wang ,&nbsp;Jian Huang ,&nbsp;Jie Zang ,&nbsp;Xueqin Jin ,&nbsp;Nieng Yan","doi":"10.1016/j.cbpa.2024.102546","DOIUrl":"10.1016/j.cbpa.2024.102546","url":null,"abstract":"","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102546"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Synthetic ion channels in biomembranes 生物膜中的合成离子通道。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-11-20 DOI: 10.1016/j.cbpa.2024.102544
Ai Kohata , Kazushi Kinbara
{"title":"Synthetic ion channels in biomembranes","authors":"Ai Kohata ,&nbsp;Kazushi Kinbara","doi":"10.1016/j.cbpa.2024.102544","DOIUrl":"10.1016/j.cbpa.2024.102544","url":null,"abstract":"<div><div>Ion transport across cell membranes is crucial in maintaining ion homeostasis in cells. Synthetic molecules that can mimic the functions of natural ion channel proteins would possess great potential as therapeutic agents by promoting apoptosis or interfering with autophagic processes through perturbing the intracellular pH or inducing oxidative and osmotic stresses. However, little is known about the underlying mechanisms in terms of direct correlation between ion transport and biological functions. This review summarizes recent progress in the area of synthetic transmembrane ion transport systems, focusing on the channel type, with an emphasis on their bioapplications as anticancer agents.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102544"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Illuminating anions in biology with genetically encoded fluorescent biosensors 用基因编码荧光生物传感器照亮生物学中的阴离子。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-12-09 DOI: 10.1016/j.cbpa.2024.102548
Mariah A. Cook , Shelby M. Phelps , Jasmine N. Tutol , Derik A. Adams, Sheel C. Dodani
{"title":"Illuminating anions in biology with genetically encoded fluorescent biosensors","authors":"Mariah A. Cook ,&nbsp;Shelby M. Phelps ,&nbsp;Jasmine N. Tutol ,&nbsp;Derik A. Adams,&nbsp;Sheel C. Dodani","doi":"10.1016/j.cbpa.2024.102548","DOIUrl":"10.1016/j.cbpa.2024.102548","url":null,"abstract":"<div><div>Anions are critical to all life forms. Anions can be absorbed as nutrients or biosynthesized. Anions shape a spectrum of fundamental biological processes at the organismal, cellular, and subcellular scales. Genetically encoded fluorescent biosensors can capture anions in action across time and space dimensions with microscopy. The firsts of such technologies were reported more than 20 years for monoatomic chloride and polyatomic cAMP anions. However, the recent boom of anion biosensors illuminates the unknowns and opportunities that remain for toolmakers and end users to meet across the aisle to spur innovations in biosensor designs and applications for discovery anion biology. In this review, we will canvas progress made over the last three years for biologically relevant anions that are classified as halides, oxyanions, carboxylates, and nucleotides.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102548"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Foldamer-mediated transport across phospholipid bilayers 折叠体介导的磷脂双层转运
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-11-30 DOI: 10.1016/j.cbpa.2024.102549
Iqra Zubair , Luis Martínez-Crespo , Simon J. Webb
{"title":"Foldamer-mediated transport across phospholipid bilayers","authors":"Iqra Zubair ,&nbsp;Luis Martínez-Crespo ,&nbsp;Simon J. Webb","doi":"10.1016/j.cbpa.2024.102549","DOIUrl":"10.1016/j.cbpa.2024.102549","url":null,"abstract":"<div><div>Crucial physiological processes, like neural communication and muscle contraction, are mediated by protein channels in cell membranes. These natural channels typically have a central hydrophilic pore with tightly defined dimensions, which can be opened or closed (‘gated’) by external stimuli. Mimicking natural ion channels using synthetic molecules is a long-standing goal in artificial channel research. Although current synthetic channels have not yet achieved the same combination of high activity, high selectivity, and gating as natural channels, foldamers offer a new approach. Foldamers are unnatural oligomers that fold into defined three-dimensional shapes, similar to the way that natural polypeptides fold into secondary structures. With defined shapes and often multi-nanometre dimensions, foldamers have become valuable tools to mimic the behaviour of natural proteins in membranes. This review highlights selected recent examples of foldamer channels, examples that indicate how foldamer architectures may lead to controllable channels with high activity and selectivity.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102549"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Enabling structural biological electron paramagnetic resonance spectroscopy in membrane proteins through spin labelling 通过自旋标记实现膜蛋白结构生物电子顺磁共振波谱。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-12-21 DOI: 10.1016/j.cbpa.2024.102564
Anokhi Shah , Joshua L. Wort , Yue Ma , Christos Pliotas
{"title":"Enabling structural biological electron paramagnetic resonance spectroscopy in membrane proteins through spin labelling","authors":"Anokhi Shah ,&nbsp;Joshua L. Wort ,&nbsp;Yue Ma ,&nbsp;Christos Pliotas","doi":"10.1016/j.cbpa.2024.102564","DOIUrl":"10.1016/j.cbpa.2024.102564","url":null,"abstract":"<div><div>Pulsed dipolar electron paramagnetic resonance spectroscopy (PDS), combined with site-directed spin-labelling, represents a powerful tool for the investigation of biomacromolecules, emerging as a keystone approach in structural biology. Increasingly, PDS is applied to study highly complex integral membrane protein systems, such as mechanosensitive ion channels, transporters, G-protein coupled receptors, ion pumps, and outer membrane proteins elucidating their dynamics and revealing conformational ensembles. Indeed, PDS offers a platform to study intermediate or lowly-populated states that are otherwise invisible to other modern methods, such as X-ray crystallography, cryo-EM, and hydrogen-deuterium exchange-mass spectrometry. Importantly, advances in spin labelling strategies welcome a new era of membrane protein investigation under near-native or in-cell conditions. Here, we review recent integral membrane protein PDS applications, and highlight well-suited, emerging spin labelling strategies that show promise for future studies.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102564"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Discovering microbiota functions via chemical probe incorporation for targeted sequencing 通过化学探针结合发现微生物群功能，用于靶向测序
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-11-30 DOI: 10.1016/j.cbpa.2024.102551
Natalie Falco , Matthew E. Griffin
{"title":"Discovering microbiota functions via chemical probe incorporation for targeted sequencing","authors":"Natalie Falco ,&nbsp;Matthew E. Griffin","doi":"10.1016/j.cbpa.2024.102551","DOIUrl":"10.1016/j.cbpa.2024.102551","url":null,"abstract":"<div><div>Our microbiota plays crucial roles in immune development and homeostasis and has been implicated in virtually all major diseases of the 21st century. Nevertheless, our understanding of the exact microbial functions that underlie these correlations remains extremely limited, due in large part to the difficulty of profiling cellular activities within non-model organisms and complex communities. Over the past decade, new flow cytometric approaches have been developed to distinguish specific microbial populations based on their interactions with metabolite analogs, modified biomolecules, and reactive compounds. By selecting and separating active microbes via fluorescence-activated cell sorting, PRobe INcorporation for Targeted sequencing (PRINT-seq) has inspired innovative approaches to identify and characterize functional members of our microbiota. Here, we provide a broad overview of this evolving technology and summarize how this method has been recently employed as a diagnostic fingerprint for diverse microbial activities.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102551"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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