Pub Date : 2025-06-01Epub Date: 2025-03-20DOI: 10.1016/j.cbpa.2025.102586
Salvatore La Gatta, Vincent L. Pecoraro
Advances in de novo design of metallopeptides have paved the way for customized metalloenzyme mimics with impressive catalytic capabilities. Over the last few years, incorporation of transition metals into simplified peptide scaffolds has allowed for catalytic efficiencies similar to or greater than those found in natural metalloenzymes. Artificial de novo peptide scaffolds highlight how precise modifications to metal coordination environments can improve scaffold stability and catalytic efficiency for a wide range of applications towards redox, non redox, synthetic, and energy conversion chemistry. These insights deepen our understanding of enzyme evolution and set a solid foundation for new directions in biocatalysis.
{"title":"Recent advances in de novo designed metallopeptides as tailored enzyme mimics","authors":"Salvatore La Gatta, Vincent L. Pecoraro","doi":"10.1016/j.cbpa.2025.102586","DOIUrl":"10.1016/j.cbpa.2025.102586","url":null,"abstract":"<div><div>Advances in <em>de novo</em> design of metallopeptides have paved the way for customized metalloenzyme mimics with impressive catalytic capabilities. Over the last few years, incorporation of transition metals into simplified peptide scaffolds has allowed for catalytic efficiencies similar to or greater than those found in natural metalloenzymes. Artificial <em>de novo</em> peptide scaffolds highlight how precise modifications to metal coordination environments can improve scaffold stability and catalytic efficiency for a wide range of applications towards redox, non redox, synthetic, and energy conversion chemistry. These insights deepen our understanding of enzyme evolution and set a solid foundation for new directions in biocatalysis.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"86 ","pages":"Article 102586"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673039","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}
Pub Date : 2025-06-01Epub Date: 2025-03-12DOI: 10.1016/j.cbpa.2025.102584
Sigridur G. Suman
Functional mimics of enzymes have a long history with bioinorganic chemists. Early motivation for creating these mimics was strongly based on the study of the enzyme reaction mechanisms. In more recent times, interest in functional mimics has expanded to catalytic metallodrugs, where the mimics are deliberately designed for specific catalytic reactions intended for therapeutic purposes. In vivo, noncytotoxic catalysis targets reactions designed to activate prodrugs. Natural or de novo proteins were developed for artificial enzyme catalysis of Diels–Alder reactions, or as artificial oxygenase mimics. Novel sulfur-rich catalytic superoxide dismutase (SOD) mimics were discovered as antioxidants. Detoxification of elevated levels of cyanide where the natural rhodanese enzyme becomes inefficient in turnover rates and bioavailability is particularly attractive for sulfur-rich molybdenum clusters. This brief overview includes metal catalysts performing abiotic reactions in vivo disguised by attachment to cell surfaces, as artificial enzymes, and interesting new sulfur-rich complexes performing SOD reactions or neutralizing cyanide.
{"title":"Noncytotoxic catalytic enzyme functional mimics including cyanide poisoning antidotes","authors":"Sigridur G. Suman","doi":"10.1016/j.cbpa.2025.102584","DOIUrl":"10.1016/j.cbpa.2025.102584","url":null,"abstract":"<div><div>Functional mimics of enzymes have a long history with bioinorganic chemists. Early motivation for creating these mimics was strongly based on the study of the enzyme reaction mechanisms. In more recent times, interest in functional mimics has expanded to catalytic metallodrugs, where the mimics are deliberately designed for specific catalytic reactions intended for therapeutic purposes. <em>In vivo,</em> noncytotoxic catalysis targets reactions designed to activate prodrugs. Natural or <em>de novo</em> proteins were developed for artificial enzyme catalysis of Diels–Alder reactions, or as artificial oxygenase mimics. Novel sulfur-rich catalytic superoxide dismutase (SOD) mimics were discovered as antioxidants. Detoxification of elevated levels of cyanide where the natural rhodanese enzyme becomes inefficient in turnover rates and bioavailability is particularly attractive for sulfur-rich molybdenum clusters. This brief overview includes metal catalysts performing abiotic reactions <em>in vivo</em> disguised by attachment to cell surfaces, as artificial enzymes, and interesting new sulfur-rich complexes performing SOD reactions or neutralizing cyanide.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"86 ","pages":"Article 102584"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609929","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}
Pub Date : 2025-06-01Epub Date: 2025-04-19DOI: 10.1016/j.cbpa.2025.102596
Alyssa M. Carter , Emily C. Woods , Matthew Bogyo
Microbial pathogens continue to plague human health and develop resistance to our current frontline treatments. Over the last few decades, there has been limited development of antibiotics with new mechanisms of action, highlighting our need to identify processes that can be targeted by next generation therapeutics. Recent advancements in our understanding of the roles that lipids play in key bacterial processes suggest that these biomolecules are a potentially valuable site for disruption by therapeutic agents. Specifically, the success of a pathogen depends on its ability to make fatty acids de novo or scavenge lipids from its host. This review focuses on recent advances using chemical biology tools for defining and disrupting lipid pathways in bacteria.
{"title":"Chemical strategies for targeting lipid pathways in bacterial pathogens","authors":"Alyssa M. Carter , Emily C. Woods , Matthew Bogyo","doi":"10.1016/j.cbpa.2025.102596","DOIUrl":"10.1016/j.cbpa.2025.102596","url":null,"abstract":"<div><div>Microbial pathogens continue to plague human health and develop resistance to our current frontline treatments. Over the last few decades, there has been limited development of antibiotics with new mechanisms of action, highlighting our need to identify processes that can be targeted by next generation therapeutics. Recent advancements in our understanding of the roles that lipids play in key bacterial processes suggest that these biomolecules are a potentially valuable site for disruption by therapeutic agents. Specifically, the success of a pathogen depends on its ability to make fatty acids <em>de novo</em> or scavenge lipids from its host. This review focuses on recent advances using chemical biology tools for defining and disrupting lipid pathways in bacteria.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"86 ","pages":"Article 102596"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850137","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}
Pub Date : 2025-06-01Epub Date: 2025-04-04DOI: 10.1016/j.cbpa.2025.102595
Lanxin Li, Yuan Qiao
The growing global prevalence of drug-resistant fungal infections and the scarcity of effective clinical antifungal drugs necessitate an urgent need for new treatments and strategies. In the quest for novel antifungal and anti-virulence compounds and alternative drug targets in fungi, we recognize the significant value of chemical biology tools in guiding these endeavors. Focusing on Candida albicans, the major fungal pathogen in humans, this review explores recent antifungal research efforts that utilize chemical biology tools—such as chemical probes and toolkits—that offer valuable biological insights into the cellular processes of C. albicans. In addition, we discuss the wealth of compounds in the host gut microbiota that naturally influence C. albicans invasive growth in the gut habitat, presenting promising yet underexplored opportunities for developing novel antifungal and anti-virulence strategies. Chemical biology tools are uniquely positioned to unlock the potential of gut microbiota-derived molecules and metabolites in combating C. albicans infections.
{"title":"Opportunities in exploring chemical biology tools for better strategies against Candida albicans","authors":"Lanxin Li, Yuan Qiao","doi":"10.1016/j.cbpa.2025.102595","DOIUrl":"10.1016/j.cbpa.2025.102595","url":null,"abstract":"<div><div>The growing global prevalence of drug-resistant fungal infections and the scarcity of effective clinical antifungal drugs necessitate an urgent need for new treatments and strategies. In the quest for novel antifungal and anti-virulence compounds and alternative drug targets in fungi, we recognize the significant value of chemical biology tools in guiding these endeavors. Focusing on <em>Candida albicans</em>, the major fungal pathogen in humans, this review explores recent antifungal research efforts that utilize chemical biology tools—such as chemical probes and toolkits—that offer valuable biological insights into the cellular processes of <em>C. albicans</em>. In addition, we discuss the wealth of compounds in the host gut microbiota that naturally influence <em>C. albicans</em> invasive growth in the gut habitat, presenting promising yet underexplored opportunities for developing novel antifungal and anti-virulence strategies. Chemical biology tools are uniquely positioned to unlock the potential of gut microbiota-derived molecules and metabolites in combating <em>C. albicans</em> infections.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"86 ","pages":"Article 102595"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769109","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}
Pub Date : 2025-06-01Epub Date: 2025-03-26DOI: 10.1016/j.cbpa.2025.102594
Michael J. Smanski , Ryan M. Peterson , Sheng-Xiong Huang , Ben Shen
{"title":"Corrigendum to “Bacterial diterpene synthases: New opportunities for mechanistic enzymology and engineered biosynthesis” [Curr Opin Chem Biol, 16 (2012) 132–141","authors":"Michael J. Smanski , Ryan M. Peterson , Sheng-Xiong Huang , Ben Shen","doi":"10.1016/j.cbpa.2025.102594","DOIUrl":"10.1016/j.cbpa.2025.102594","url":null,"abstract":"","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"86 ","pages":"Article 102594"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698155","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}
Pub Date : 2025-06-01Epub Date: 2025-03-20DOI: 10.1016/j.cbpa.2025.102585
Priscilla Dzigba , Megan A. Seth , Mallary C. Greenlee-Wacker , Benjamin M. Swarts
The increasing prevalence of antibiotic resistance, the stagnation of antibiotic development, and the adaptive capacity of bacteria to subvert the host immune response combine to pose significant global health concerns. Consequently, there is an urgent need to develop alternative therapeutic approaches to combat bacterial infections. Antibody-recruiting molecules (ARMs), which are bispecific small molecules that recruit endogenous antibodies to pathogenic cells or viruses, offer a promising avenue to harness the host immune system to target various diseases. In this review, we cover ARM strategies that have been developed for bacterial pathogens, including Gram-positive bacteria, Gram-negative bacteria, and mycobacteria, and we discuss the prospects and challenges of utilizing ARMs as alternatives to traditional antibiotic therapies.
{"title":"Redirecting the host immune response to bacterial infection with antibody-recruiting molecules (ARMs)","authors":"Priscilla Dzigba , Megan A. Seth , Mallary C. Greenlee-Wacker , Benjamin M. Swarts","doi":"10.1016/j.cbpa.2025.102585","DOIUrl":"10.1016/j.cbpa.2025.102585","url":null,"abstract":"<div><div>The increasing prevalence of antibiotic resistance, the stagnation of antibiotic development, and the adaptive capacity of bacteria to subvert the host immune response combine to pose significant global health concerns. Consequently, there is an urgent need to develop alternative therapeutic approaches to combat bacterial infections. Antibody-recruiting molecules (ARMs), which are bispecific small molecules that recruit endogenous antibodies to pathogenic cells or viruses, offer a promising avenue to harness the host immune system to target various diseases. In this review, we cover ARM strategies that have been developed for bacterial pathogens, including Gram-positive bacteria, Gram-negative bacteria, and mycobacteria, and we discuss the prospects and challenges of utilizing ARMs as alternatives to traditional antibiotic therapies.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"86 ","pages":"Article 102585"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673084","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}
Pub Date : 2025-04-01Epub Date: 2025-02-03DOI: 10.1016/j.cbpa.2025.102569
Tianlu Wang , Tatsuki Nonomura , Tien-Hung Lan , Yubin Zhou
Optogenetics, which integrates photonics and genetic engineering to control protein activity and cellular processes, has transformed biomedical research. Its precise spatiotemporal control, minimal invasiveness, and tunable reversibility have spurred its widespread adoption in both basic and clinical research. Optogenetic techniques have been applied to partially restore vision in blind patients and are being actively explored as innovative treatments for neurological, psychiatric, cardiac, and immunological disorders. Microbial channelrhodopsins (ChRs) allow precise manipulation of neuronal and cardiac activities, while vertebrate rhodopsins offer unique opportunities for ion channel modulation through G-protein-coupled receptor (GPCR) pathways. Plant-derived photoswitchable domains can also be engineered into ion channels to confer photosensitivity. This review summarizes the latest progress in engineering genetically encoded light-sensitive ion channel actuators and modulators (GELICAMs) with diverse ion selectivity and spectral sensitivity. We further discuss the potential applications and challenges of these tools in advancing biomedical research and therapeutic interventions.
{"title":"Optogenetic engineering for ion channel modulation","authors":"Tianlu Wang , Tatsuki Nonomura , Tien-Hung Lan , Yubin Zhou","doi":"10.1016/j.cbpa.2025.102569","DOIUrl":"10.1016/j.cbpa.2025.102569","url":null,"abstract":"<div><div>Optogenetics, which integrates photonics and genetic engineering to control protein activity and cellular processes, has transformed biomedical research. Its precise spatiotemporal control, minimal invasiveness, and tunable reversibility have spurred its widespread adoption in both basic and clinical research. Optogenetic techniques have been applied to partially restore vision in blind patients and are being actively explored as innovative treatments for neurological, psychiatric, cardiac, and immunological disorders. Microbial channelrhodopsins (ChRs) allow precise manipulation of neuronal and cardiac activities, while vertebrate rhodopsins offer unique opportunities for ion channel modulation through G-protein-coupled receptor (GPCR) pathways. Plant-derived photoswitchable domains can also be engineered into ion channels to confer photosensitivity. This review summarizes the latest progress in engineering genetically encoded light-sensitive ion channel actuators and modulators (GELICAMs) with diverse ion selectivity and spectral sensitivity. We further discuss the potential applications and challenges of these tools in advancing biomedical research and therapeutic interventions.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"85 ","pages":"Article 102569"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132999","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}
Pub Date : 2025-04-01Epub Date: 2025-03-03DOI: 10.1016/j.cbpa.2025.102582
Sandip Chattopadhayay, Pinaki Talukdar
Nature endowed different structurally and functionally complex transmembrane transporters to flux the ions to maintain the healthy functions of the cells by turning on or turning off the ion flow in the presence of external stimuli. Mimicking this stimuli-responsive behavior of natural transporters using synthetic analogs is currently an ongoing interest in the scientific community. This short review highlights the recent development of synthetic responsive ionophore systems. This includes pH, light, redox, enzyme, and multi-stimuli-controlled ionophores systems that have the potential to be utilized in different biomedical applications ranging from antibacterial activity to anticancer activity.
{"title":"Stimuli-responsive synthetic ionophores for therapeutic applications","authors":"Sandip Chattopadhayay, Pinaki Talukdar","doi":"10.1016/j.cbpa.2025.102582","DOIUrl":"10.1016/j.cbpa.2025.102582","url":null,"abstract":"<div><div>Nature endowed different structurally and functionally complex transmembrane transporters to flux the ions to maintain the healthy functions of the cells by turning on or turning off the ion flow in the presence of external stimuli. Mimicking this stimuli-responsive behavior of natural transporters using synthetic analogs is currently an ongoing interest in the scientific community. This short review highlights the recent development of synthetic responsive ionophore systems. This includes pH, light, redox, enzyme, and multi-stimuli-controlled ionophores systems that have the potential to be utilized in different biomedical applications ranging from antibacterial activity to anticancer activity.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"85 ","pages":"Article 102582"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534456","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}
Pub Date : 2025-04-01Epub Date: 2025-02-19DOI: 10.1016/j.cbpa.2025.102581
Helene Jahn , Show-Ling Shyng , Carsten Schultz
Lipids can have specific interaction partners and act as small molecule regulators of proteins, especially for transmembrane proteins. Transmembrane proteins, such as ion channels, can be influenced by lipids in four ways; lipids can be direct ligands, localize effector proteins or domains, affect protein–protein interaction, or change the biophysical properties of the surrounding membrane. In this article, we will give examples of how lipids directly interact with ion channels and address the complex aspect of indirect regulation via lipids of the surrounding membrane bilayer. In addition, we discuss current and propose future molecular tools and experiments elucidating the many roles lipids play in ion channel function.
{"title":"Lipid probes to study ion channels","authors":"Helene Jahn , Show-Ling Shyng , Carsten Schultz","doi":"10.1016/j.cbpa.2025.102581","DOIUrl":"10.1016/j.cbpa.2025.102581","url":null,"abstract":"<div><div>Lipids can have specific interaction partners and act as small molecule regulators of proteins, especially for transmembrane proteins. Transmembrane proteins, such as ion channels, can be influenced by lipids in four ways; lipids can be direct ligands, localize effector proteins or domains, affect protein–protein interaction, or change the biophysical properties of the surrounding membrane. In this article, we will give examples of how lipids directly interact with ion channels and address the complex aspect of indirect regulation via lipids of the surrounding membrane bilayer. In addition, we discuss current and propose future molecular tools and experiments elucidating the many roles lipids play in ion channel function.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"85 ","pages":"Article 102581"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445707","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}
Pub Date : 2025-04-01Epub Date: 2025-02-26DOI: 10.1016/j.cbpa.2025.102583
Anokhi Shah , Joshua L. Wort , Yue Ma , Christos Pliotas
{"title":"Corrigendum to “Enabling structural biological electron paramagnetic resonance spectroscopy in membrane proteins through spin labelling” Curr Opin Chem Biol 84 (2025) 102564","authors":"Anokhi Shah , Joshua L. Wort , Yue Ma , Christos Pliotas","doi":"10.1016/j.cbpa.2025.102583","DOIUrl":"10.1016/j.cbpa.2025.102583","url":null,"abstract":"","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"85 ","pages":"Article 102583"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487537","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}
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