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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 : 2024-09-27 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":"2024-09-27","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
Endogenous electrophiles and peroxymonocarbonate can link tyrosine phosphorylation cascades with the cytosolic TXNRD1 selenoprotein and the KEAP1/NRF2 system 内源性亲电子物和过氧碳酸氢盐可将酪氨酸磷酸化级联与细胞质 TXNRD1 硒蛋白和 KEAP1/NRF2 系统联系起来。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-09-06 DOI: 10.1016/j.cbpa.2024.102522
Markus Dagnell , Elias S.J. Arnér
{"title":"Endogenous electrophiles and peroxymonocarbonate can link tyrosine phosphorylation cascades with the cytosolic TXNRD1 selenoprotein and the KEAP1/NRF2 system","authors":"Markus Dagnell ,&nbsp;Elias S.J. Arnér","doi":"10.1016/j.cbpa.2024.102522","DOIUrl":"10.1016/j.cbpa.2024.102522","url":null,"abstract":"<div><p>Endogenously formed reactive molecules, such as lipid peroxides, 4-hydroxynonenal, methylglyoxal and other reactive oxygen species, can have major effects on cells. Accumulation of these molecules is counteracted by antioxidant enzymes, including the glutathione (GSH) and thioredoxin (Trx) systems, in turn regulated by the KEAP1/NRF2 system. Receptor tyrosine kinases (RTK) and their counteracting protein tyrosine phosphatases (PTP) are also modulated through redox regulation of PTP activities. The cytosolic selenoprotein thioredoxin reductase (TXNRD1) is particularly prone to attack at its easily accessible catalytic selenocysteine (Sec) residue by reactive electrophilic compounds. Therefore, we here discuss how endogenously formed electrophiles can modulate RTK/PTP signaling in a concentration- and time dependent manner by reactions either directly or indirectly linking TXNRD1 with the KEAP1/NRF2 system. Moreover, recent findings suggest that endogenous formation of peroxymonocarbonate can efficiently inhibit PTP activities and stimulate RTK signaling, seemingly bypassing PTP reduction as otherwise supported by the GSH/Trx systems.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102522"},"PeriodicalIF":6.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S136759312400098X/pdfft?md5=a310db9e055eef46580e7b9e5c96a3b4&pid=1-s2.0-S136759312400098X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144529","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 : 2024-09-02 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":"2024-09-02","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
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 : 2024-08-29 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":"2024-08-29","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 : 2024-08-13 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":"2024-08-13","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
From the forest floor to the lab: Insights into the diversity and complexity of mushroom polyketide synthases 从林地到实验室：洞察蘑菇多酮合成酶的多样性和复杂性。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-10 DOI: 10.1016/j.cbpa.2024.102510
Nikolai A. Löhr , Lukas Platz , Dirk Hoffmeister , Michael Müller
{"title":"From the forest floor to the lab: Insights into the diversity and complexity of mushroom polyketide synthases","authors":"Nikolai A. Löhr ,&nbsp;Lukas Platz ,&nbsp;Dirk Hoffmeister ,&nbsp;Michael Müller","doi":"10.1016/j.cbpa.2024.102510","DOIUrl":"10.1016/j.cbpa.2024.102510","url":null,"abstract":"<div><p>Mushroom-forming fungi exhibit a distinctive ecology, which is unsurprisingly also reflected in unique and divergent biosynthetic pathways. We review this phenomenon through the lens of the polyketide metabolism, where mushrooms often deviate from established principles and challenge conventional paradigms. This is evident not only by non-canonical enzyme architectures and functions but also by their propensity for multi-product synthases rather than single-product pathways. Nevertheless, mushrooms also feature many polyketides familiar from plants, bacteria, and fungi of their sister division Ascomycota, which, however, are the result of an independent evolution. In this regard, the captivating biosynthetic pathways of mushrooms might even help us understand the biological pressures that led to the simultaneous production of the same natural products (via convergent evolution, co-evolution, and/or metaevolution) and thus address the question of their <em>raison d'être</em>.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"82 ","pages":"Article 102510"},"PeriodicalIF":6.9,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000863/pdfft?md5=fa57ba35ff5b4bbb74531c3b64a4107a&pid=1-s2.0-S1367593124000863-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915684","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
Glycoengineering in antigen-specific immunotherapies 抗原特异性免疫疗法中的糖工程。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 DOI: 10.1016/j.cbpa.2024.102503
Yuxin Li , Hongming Chen , Jiuxiang Gao , Peng Wu , Senlian Hong
{"title":"Glycoengineering in antigen-specific immunotherapies","authors":"Yuxin Li ,&nbsp;Hongming Chen ,&nbsp;Jiuxiang Gao ,&nbsp;Peng Wu ,&nbsp;Senlian Hong","doi":"10.1016/j.cbpa.2024.102503","DOIUrl":"10.1016/j.cbpa.2024.102503","url":null,"abstract":"<div><p>Advances in immunotherapy have revolutionized modern medical care paradigms. However, many patients respond poorly to the current FDA-approved treatment regimens that primarily target protein-based antigens or checkpoints. Current progress in developing therapeutic strategies that target disease-associated glycans has pinpointed a new class of glycoimmune checkpoints that function orthogonally to the established protein-immune checkpoints. Glycoengineering using chemical, enzymatic, and genetic methods is also increasingly recognized for its massive potential to improve biopharmaceuticals, such as tailoring therapies with antigen-targeting agents. Here, we review the recent development and applications of glycoengineering of antibodies and cells to suit therapeutic applications. We highlight living-cell glycoengineering strategies on cancer and immune cells for better therapeutic efficacy against specific antigens by leveraging the pre-existing immune machinery or instructing <em>de novo</em> creation of targeting agents. We also discuss glycoengineering strategies for studying basic immuno-oncology. Collectively, glycoengineering has a significant contribution to the design of antigen-specific immunotherapies.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102503"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756041","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 progresses in the cyclization and oxidation of polyketide biosynthesis 多酮生物合成的环化和氧化的最新进展。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 DOI: 10.1016/j.cbpa.2024.102507
Bo Zhang, Hui Ming Ge
{"title":"Recent progresses in the cyclization and oxidation of polyketide biosynthesis","authors":"Bo Zhang,&nbsp;Hui Ming Ge","doi":"10.1016/j.cbpa.2024.102507","DOIUrl":"10.1016/j.cbpa.2024.102507","url":null,"abstract":"<div><p>Polyketides represent an important class of natural products, renowned for their intricate structures and diverse biological activities. In contrast to common fatty acids, polyketides possess relatively more rigid carbon skeletons, more complex ring systems, and chiral centers. These structural features are primarily achieved through distinctive enzymatic cyclizations and oxidations as tailoring steps. In this opinion, we discuss the recent progress in deciphering the mechanisms of cyclization and oxidation within polyketide biosynthesis. By shedding light on these enzymatic processes, this article seeks to motivate the community to unravel the remaining mysteries surrounding cyclase and oxidase functionalities and to explore novel polyketide natural products through genome mining.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102507"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887844","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
Strategies and mechanisms for endosomal escape of therapeutic nucleic acids 治疗性核酸的内体逸出策略和机制。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 DOI: 10.1016/j.cbpa.2024.102506
Melina Grau , Ernst Wagner
{"title":"Strategies and mechanisms for endosomal escape of therapeutic nucleic acids","authors":"Melina Grau ,&nbsp;Ernst Wagner","doi":"10.1016/j.cbpa.2024.102506","DOIUrl":"10.1016/j.cbpa.2024.102506","url":null,"abstract":"<div><p>Despite impressive recent establishment of therapeutic nucleic acids as drugs and vaccines, their broader medical use is impaired by modest performance in intracellular delivery. Inefficient endosomal escape presents a major limitation responsible for inadequate cytosolic cargo release. Depending on the carrier, this endosomal barrier can strongly limit or even abolish nucleic acid delivery. Different recent endosomal escape strategies and their hypothesized mechanisms are reviewed.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102506"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000826/pdfft?md5=2b89c2b69ecf385ac782b8ed8112060e&pid=1-s2.0-S1367593124000826-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887845","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
Discovery and evolution of [4 + 2] cyclases 4 + 2] 环酶的发现与进化。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 DOI: 10.1016/j.cbpa.2024.102504
Jiawang Liu, Youcai Hu
{"title":"Discovery and evolution of [4 + 2] cyclases","authors":"Jiawang Liu,&nbsp;Youcai Hu","doi":"10.1016/j.cbpa.2024.102504","DOIUrl":"10.1016/j.cbpa.2024.102504","url":null,"abstract":"<div><p>[4 + 2] Cyclases are potent biocatalysts that have been bestowed upon microorganisms and plants by nature, equipping them with the powerful tools to utilize and implement the [4 + 2] cycloaddition reaction for constructing the cyclohexene core in synthesizing valuable molecules. Over the past two years, eleven new enzymes have joined this pericyclase club and undergone extensive investigation. In this review, we present a comprehensive overview of recent advancements in characterizing [4 + 2] cyclases with regard to their catalytic mechanism and stereoselectivity. We particularly focus on insights gained from enzyme co–crystal structures, cofactors, as well as the effects of glycosylation. Advancements in understanding the mechanisms of natural [4 + 2] cyclases offer the potential to mimic evolutionary processes and engineer artificial enzymes for the development of valuable and practical biocatalysts.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102504"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786753","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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