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Current Opinion in Chemical Biology最新文献

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Bacterial peptidoglycan as a living polymer.
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub 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, Jed F Fisher, Shahriar Mobashery","doi":"10.1016/j.cbpa.2024.102562","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102562","url":null,"abstract":"<p><p>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 via recycling processes and as signaling molecules. Cell-wall recycling and de novo 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.</p>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"102562"},"PeriodicalIF":6.9,"publicationDate":"2024-12-18","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
Illuminating anions in biology with genetically encoded fluorescent biosensors.
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub 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, Shelby M Phelps, Jasmine N Tutol, Derik A Adams, Sheel C Dodani","doi":"10.1016/j.cbpa.2024.102548","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102548","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"102548"},"PeriodicalIF":6.9,"publicationDate":"2024-12-09","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
Advances in acid-degradable and enzyme-cleavable linkers for drug delivery.
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-05 DOI: 10.1016/j.cbpa.2024.102552
Sheng Zhao, Na Yu, Hesong Han, Shutao Guo, Niren Murthy
{"title":"Advances in acid-degradable and enzyme-cleavable linkers for drug delivery.","authors":"Sheng Zhao, Na Yu, Hesong Han, Shutao Guo, Niren Murthy","doi":"10.1016/j.cbpa.2024.102552","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102552","url":null,"abstract":"<p><p>Drug delivery vectors have the potential to improve the efficacy of therapeutics, including small molecules and nucleic acid-based drugs. However, challenges remain in developing linkages that enable the precise and efficient release of therapeutic cargo in response to mildly acidic environments or lysosomal enzymes. This review highlights recent advances in acid-degradable acetal/ketal and enzyme-cleavable linkages for endolysosomal release. These innovations include the developments of azido-acetal linkers with improved stability and hydrolysis kinetics, organocatalytic trans-isopropenylation for synthesizing asymmetric ketals and their applications in drug delivery, and enzyme-cleavable linkers activated by cathepsin B or β-galactosidase.</p>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"102552"},"PeriodicalIF":6.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789441","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
Development of novel indicators and molecular systems for calcium sensing through protein engineering.
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-04 DOI: 10.1016/j.cbpa.2024.102547
Alicia Climent-Catala, Mateo I Sanchez
{"title":"Development of novel indicators and molecular systems for calcium sensing through protein engineering.","authors":"Alicia Climent-Catala, Mateo I Sanchez","doi":"10.1016/j.cbpa.2024.102547","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102547","url":null,"abstract":"<p><p>Intracellular calcium (Ca<sup>2+</sup>) is involved in a plethora of cell signalling processes and physiological functions. Increases in Ca<sup>2+</sup> concentration are bona fide biomarkers of neuronal activity, reflecting the spike count, timing, frequency, and the intensity of synaptic input. The development of genetically encoded calcium indicators (GECIs) was a significant advancement in modern neuroscience that enabled real-time visualisation of neuronal activity at single-cell resolution. These indicators leverage the conformational changes induced by calcium-binding proteins, such as calmodulin (CaM) or troponin C (TnC). Harnessing protein engineering approaches such as directed evolution yielded new GECIs with enhanced sensitivity, kinetics, and brightness. Notably, the development of calcium-based integrators, such as scFLARE (single-chain fast light- and activity-regulated expression), convert transient raises in cytosolic Ca<sup>2+</sup> into a transcriptional readout rather than an optical signal. This review summarises the latest efforts in protein engineering to develop new indicators and molecular systems to sense changes in Ca<sup>2+</sup> concentrations.</p>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"102547"},"PeriodicalIF":6.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783566","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
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub 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":"2024-11-30","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
Discovering microbiota functions via chemical probe incorporation for targeted sequencing
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub 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":"2024-11-30","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
Forty sites of TRP channel regulation
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-11-30 DOI: 10.1016/j.cbpa.2024.102550
Irina A. Talyzina, Kirill D. Nadezhdin, Alexander I. Sobolevsky
{"title":"Forty sites of TRP channel regulation","authors":"Irina A. Talyzina,&nbsp;Kirill D. Nadezhdin,&nbsp;Alexander I. Sobolevsky","doi":"10.1016/j.cbpa.2024.102550","DOIUrl":"10.1016/j.cbpa.2024.102550","url":null,"abstract":"<div><div>Transient receptor potential (TRP) channels are polymodal molecular sensors that integrate chemical, thermal, mechanical and electrical stimuli and convert them into ionic currents that regulate senses of taste, smell, vision, hearing, touch and contribute to perception of temperature and pain. TRP channels are implicated in the pathogenesis of numerous human diseases, including cancers, and represent one of the most ardently pursued drug targets. Recent advances in structural biology, particularly associated with the cryo-EM “resolution revolution”, yielded numerous TRP channel structures in complex with ligands that might have therapeutic potential. In this review, we describe the recent progress in TRP channel structural biology, focusing on the description of identified binding sites for small molecules, their relationship to membrane lipids, and interaction of TRP channels with other proteins. The characterized binding sites and interfaces create a diversity of druggable targets and provide a roadmap to aid in the design of new molecules for tuning TRP channel function in disease conditions.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102550"},"PeriodicalIF":6.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746712","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
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 : 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":"2024-11-25","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
Engineered metallobiocatalysts for energy–relevant reactions 用于能源相关反应的工程金属生物催化剂
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-11-25 DOI: 10.1016/j.cbpa.2024.102545
Ryan M. Kosko , Kaye L. Kuphal , Alison A. Salamatian , Kara L. Bren
{"title":"Engineered metallobiocatalysts for energy–relevant reactions","authors":"Ryan M. Kosko ,&nbsp;Kaye L. Kuphal ,&nbsp;Alison A. Salamatian ,&nbsp;Kara L. Bren","doi":"10.1016/j.cbpa.2024.102545","DOIUrl":"10.1016/j.cbpa.2024.102545","url":null,"abstract":"<div><div>Engineering metallobiocatalysts is a promising approach to addressing challenges in energy-relevant electrocatalysis and photocatalysis. The design freedom provided by semisynthetic and fully synthetic approaches to catalyst design allows researchers to demonstrate how structural modifications can improve selectivity and activity of biocatalysts. Furthermore, the provision of a superstructure in many metallobiocatalysts facilitates active-site microenvironment engineering. Recurring themes include the role of the biomolecular scaffold in enhancing reactivity in water and catalyst robustness, the impact of the outer sphere on reactivity, and the importance of tuning system components in full system optimization. In this perspective, recent strategies to design and modify novel biocatalysts, understand proton and electron transfer mechanisms, and tune system activity by modifying catalysts and system conditions are highlighted within the field of energy-related catalysis. Opportunities in this field include developing robust structure–function relationships to support approaches to engineering second-sphere interactions and identifying ways to enhance biocatalyst activity over time.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102545"},"PeriodicalIF":6.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700373","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 : 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":"2024-11-20","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
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