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Transferring enzyme features to molecular CO2 reduction catalysts 将酶的特性转化为分子二氧化碳还原催化剂。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-11-15 DOI: 10.1016/j.cbpa.2024.102540
Matthias Huber, Corinna R. Hess
{"title":"Transferring enzyme features to molecular CO2 reduction catalysts","authors":"Matthias Huber,&nbsp;Corinna R. Hess","doi":"10.1016/j.cbpa.2024.102540","DOIUrl":"10.1016/j.cbpa.2024.102540","url":null,"abstract":"<div><div>Carbon monoxide dehydrogenases and formate dehydrogenases efficiently catalyze the reduction of CO<sub>2</sub>. In both enzymes, CO<sub>2</sub> activation at the metal active site is assisted by proximate amino acids and Fe–S-clusters. Functional features of the enzyme are mimicked in molecular catalysts by redox-active ligands, acidic and charged groups in the ligand periphery, and binuclear scaffolds. These components have all improved the catalytic performance of synthetic systems. Recent studies impart a deeper understanding of the individual contributions of the various functionalities to reactivity and of their combined effects. New catalyst platforms reveal alternate pathways for CO<sub>2</sub> reduction, unique intermediates, and strategies for switching selectivity. Design of a wider array of complexes that combine different functional elements is encouraged to further optimize catalysts for CO<sub>2</sub> reduction, especially for product formation beyond CO. More diverse bimetallic catalysts are needed to better exploit metal–metal interactions for CO<sub>2</sub> conversion.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102540"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643601","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
Therapeutic synthetic anion transporters 治疗用合成阴离子转运体
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI: 10.1016/j.cbpa.2024.102535
Elba Feo, Philip A. Gale
{"title":"Therapeutic synthetic anion transporters","authors":"Elba Feo,&nbsp;Philip A. Gale","doi":"10.1016/j.cbpa.2024.102535","DOIUrl":"10.1016/j.cbpa.2024.102535","url":null,"abstract":"<div><div>This short review highlights recent examples of small-molecule anion transporters reported in the literature that have potentially useful biological activity. This includes anionophores with antibiotic or antifungal activity, anticancer activity, or the potential to treat channelopathies such as cystic fibrosis. Additionally selective and targeted anion transporters are also discussed.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102535"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327711","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
Designing small-molecule and macromolecule sensors for imaging redox-active transition metal signaling 设计用于成像氧化还原活性过渡金属信号的小分子和大分子传感器
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1016/j.cbpa.2024.102541
Aidan T. Pezacki , Jiaying Gao , Christopher J. Chang
{"title":"Designing small-molecule and macromolecule sensors for imaging redox-active transition metal signaling","authors":"Aidan T. Pezacki ,&nbsp;Jiaying Gao ,&nbsp;Christopher J. Chang","doi":"10.1016/j.cbpa.2024.102541","DOIUrl":"10.1016/j.cbpa.2024.102541","url":null,"abstract":"<div><div>Transition metals play essential roles in biology, where these nutrients regulate protein activity as active site cofactors or via metalloallostery. In contrast, dysregulation of transition metal homeostasis can lead to unique metal-dependent signaling pathways connected to aging and disease, such as cuproptosis and ferroptosis for copper- and iron-dependent cell death or cuproplasia and ferroplasia for copper- and iron-dependent cell growth and proliferation, respectively. New methods that enable detection of bioavailable transition metal pools with both metal and oxidation state specificity can help decipher their contributions to health and disease. Here we summarize recent advances in designing sensors for imaging transition metals and their applications to uncover new metal biology.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102541"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578932","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
Engineering novel adeno-associated viruses (AAVs) for improved delivery in the nervous system 设计新型腺相关病毒 (AAV)，改进在神经系统中的传输。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-09-28 DOI: 10.1016/j.cbpa.2024.102532
Ana D. Carneiro , David V. Schaffer
{"title":"Engineering novel adeno-associated viruses (AAVs) for improved delivery in the nervous system","authors":"Ana D. Carneiro ,&nbsp;David V. Schaffer","doi":"10.1016/j.cbpa.2024.102532","DOIUrl":"10.1016/j.cbpa.2024.102532","url":null,"abstract":"<div><div>Harnessing adeno-associated virus (AAV) vectors for therapeutic gene delivery has emerged as a progressively promising strategy to treat disorders of both the central nervous system (CNS) and peripheral nervous system (PNS), and there are many ongoing clinical trials. However, unique physiological and molecular characteristics of the CNS and PNS pose obstacles to efficient vector delivery, ranging from the blood-brain barrier to the diverse nature of nervous system disorders. Engineering novel AAV capsids may help overcome these ongoing challenges and maximize therapeutic transgene delivery. This article discusses strategies for innovative AAV capsid development, highlighting recent advances. Notably, advances in next generation sequencing and machine learning have sparked new approaches for capsid investigation and engineering. Furthermore, we outline future directions and additional challenges in AAV-mediated gene therapy in the CNS and PNS.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102532"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338142","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
Drug discovery targeting Nav1.8: Structural insights and therapeutic potential 以 Nav1.8 为靶点的药物发现：结构见解和治疗潜力
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-10-17 DOI: 10.1016/j.cbpa.2024.102538
Huan Wang , Jian Huang , Jie Zang , Xueqin Jin , Nieng Yan
{"title":"Drug discovery targeting Nav1.8: Structural insights and therapeutic potential","authors":"Huan Wang ,&nbsp;Jian Huang ,&nbsp;Jie Zang ,&nbsp;Xueqin Jin ,&nbsp;Nieng Yan","doi":"10.1016/j.cbpa.2024.102538","DOIUrl":"10.1016/j.cbpa.2024.102538","url":null,"abstract":"<div><div>Voltage-gated sodium (Na<sub>v</sub>) channels are crucial in transmitting action potentials in neurons. The tetrodotoxin-resistant subtype Na<sub>v</sub>1.8 is predominantly expressed in the peripheral nervous system, offering a unique opportunity to design selective inhibitors for pain relief. A number of compounds have been reported to specifically block Na<sub>v</sub>1.8. Among these, VX-548 is already in regulatory review for the treatment of moderate-to-severe acute pain and holds the promise to be the first non-opioid pain killer over the past twenty years. Recent structural studies using cryogenic electron microscopy (cryo-EM) and structure-based predictive modeling have provided unprecedented insights into the structural pharmacology of Na<sub>v</sub>1.8. In this review, we summarize the latest developments in Na<sub>v</sub>1.8-selective inhibitors, focusing on the druggable sites and mechanisms that confer subtype specificity. These structural insights highlight the potential for Na<sub>v</sub>1.8 inhibitors to deliver non-addictive pain management, thus illuminating the avenue to next-generation analgesic development.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102538"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445250","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
Catalyzing the future: recent advances in chemical synthesis using enzymes 催化未来：利用酶进行化学合成的最新进展。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-10-05 DOI: 10.1016/j.cbpa.2024.102536
Julia C. Reisenbauer , Kathleen M. Sicinski , Frances H. Arnold
{"title":"Catalyzing the future: recent advances in chemical synthesis using enzymes","authors":"Julia C. Reisenbauer ,&nbsp;Kathleen M. Sicinski ,&nbsp;Frances H. Arnold","doi":"10.1016/j.cbpa.2024.102536","DOIUrl":"10.1016/j.cbpa.2024.102536","url":null,"abstract":"<div><div>Biocatalysis has the potential to address the need for more sustainable organic synthesis routes. Protein engineering can tune enzymes to perform in cascade reactions and for efficient synthesis of enantiomerically enriched compounds, using both natural and new-to-nature reaction pathways. This review highlights recent achievements in biocatalysis, especially the development of novel enzymatic syntheses to access versatile small molecule intermediates and complex biomolecules. Biocatalytic strategies for the degradation of persistent pollutants and approaches for biomass valorization are also discussed. The transition of chemical synthesis to a greener future will be accelerated by implementing enzymes and engineering them for high performance and new activities.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102536"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379706","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
Recent advances in the expanding genetic code 扩展遗传密码的最新进展。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-10-03 DOI: 10.1016/j.cbpa.2024.102537
Michael L. Pigula, Peter G. Schultz
{"title":"Recent advances in the expanding genetic code","authors":"Michael L. Pigula,&nbsp;Peter G. Schultz","doi":"10.1016/j.cbpa.2024.102537","DOIUrl":"10.1016/j.cbpa.2024.102537","url":null,"abstract":"<div><div>For over a billion years, the central dogma of biology has been limited largely to 20 canonical amino acids with relatively simple functionalities. The ability to rationally add new building blocks to the genetic code has enabled the site-specific incorporation of hundreds of noncanonical amino acids (ncAAs) with novel properties into proteins in living organisms. Recent technological advances have enabled high level mammalian expression of proteins containing ncAAs, the use of unique codons to direct ncAA incorporation, extension of this methodology to a range of eukaryotic organisms, and the ability to encode building blocks beyond α-amino acids. These ncAAs have been used to study and control proteins in their native cellular context and to engineer enzymes and biotherapeutics with improved or novel properties. Herein we discuss recent developments in the field and potential future research directions.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102537"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374724","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
Myeloid C-type lectin receptors in host–pathogen interactions and glycan-based targeting 髓系 C 型凝集素受体在宿主-病原体相互作用和基于聚糖的靶向中的作用
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-10-01 Epub Date: 2024-08-29 DOI: 10.1016/j.cbpa.2024.102521
Felix Stegmann , Bernd Lepenies
{"title":"Myeloid C-type lectin receptors in host–pathogen interactions and glycan-based targeting","authors":"Felix Stegmann ,&nbsp;Bernd Lepenies","doi":"10.1016/j.cbpa.2024.102521","DOIUrl":"10.1016/j.cbpa.2024.102521","url":null,"abstract":"<div><p>Lectin–glycan interactions play a crucial role in the immune system. An important class of lectins in the innate immune system is myeloid C-type lectin receptors (CLRs). Myeloid CLRs act as pattern recognition receptors and are predominantly expressed by myeloid cells, such as macrophages, dendritic cells, and neutrophils. In innate immunity, CLRs contribute to self/non-self discrimination. While the recognition of pathogen-associated molecular patterns (PAMPs) by CLRs may contribute to a protective immune response, CLR engagement can also be exploited by pathogens for immune evasion. Since various CLRs act as endocytic receptors and trigger distinct signaling pathways in myeloid cells, CLR targeting has proven useful for drug/antigen delivery into antigen-presenting cells and the modulation of immune responses. This review covers recent discoveries of pathogen/CLR interactions and novel approaches for CLR targeting within the period of the past two years.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"82 ","pages":"Article 102521"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000978/pdfft?md5=306dced818d81a5ca24ab6335f230013&pid=1-s2.0-S1367593124000978-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099058","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
Neuroprotective signaling by hydrogen sulfide and its dysregulation in Alzheimer's disease 硫化氢的神经保护信号及其在阿尔茨海默病中的失调
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI: 10.1016/j.cbpa.2024.102511
Bindu D. Paul , Andrew A. Pieper
{"title":"Neuroprotective signaling by hydrogen sulfide and its dysregulation in Alzheimer's disease","authors":"Bindu D. Paul ,&nbsp;Andrew A. Pieper","doi":"10.1016/j.cbpa.2024.102511","DOIUrl":"10.1016/j.cbpa.2024.102511","url":null,"abstract":"<div><p>The ancient messenger molecule hydrogen sulfide (H<sub>2</sub>S) modulates myriad signaling cascades and has been conserved across evolutionary boundaries. Although traditionally known as an environmental toxin, H<sub>2</sub>S is also synthesized endogenously to exert modulatory and homeostatic effects in a broad array of physiologic functions. Notably, H<sub>2</sub>S levels are tightly physiologically regulated, as both its excess and paucity can be toxic. Accumulating evidence has revealed pivotal roles for H<sub>2</sub>S in neuroprotection and normal cognitive function, and H<sub>2</sub>S homeostasis is dysregulated in neurodegenerative conditions. Here, we review the normal neuroprotective roles of H<sub>2</sub>S that go awry in Alzheimer's disease, the most common form of neurodegenerative disease.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"82 ","pages":"Article 102511"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000875/pdfft?md5=e3e84ee89762b9b7024bc906392dbab2&pid=1-s2.0-S1367593124000875-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978218","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
An expanded molecular and systems toolbox for imaging, mapping, and controlling local translation 用于成像、绘图和控制局部翻译的扩展分子和系统工具箱
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-10-01 Epub Date: 2024-09-02 DOI: 10.1016/j.cbpa.2024.102523
Warunya Onchan , Chadaporn Attakitbancha , Chayasith Uttamapinant
{"title":"An expanded molecular and systems toolbox for imaging, mapping, and controlling local translation","authors":"Warunya Onchan ,&nbsp;Chadaporn Attakitbancha ,&nbsp;Chayasith Uttamapinant","doi":"10.1016/j.cbpa.2024.102523","DOIUrl":"10.1016/j.cbpa.2024.102523","url":null,"abstract":"<div><p>Localized protein translation occurs through trafficking of mRNAs and protein translation machineries to different compartments of the cell, leading to rapid on-site synthesis of proteins in response to signaling cues. The spatiotemporally precise nature of the local translation process necessitates continual developments of technologies reviewed herein to visualize and map biomolecular components and the translation process with better spatial and temporal resolution and with fewer artifacts. We also discuss approaches to control local translation, which can serve as a design paradigm for subcellular genetic devices for eukaryotic synthetic biology.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"82 ","pages":"Article 102523"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122979","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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