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Application of artificial backbone connectivity in the development of metalloenzyme mimics 应用人工骨架连接技术开发金属酶模拟物。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 DOI: 10.1016/j.cbpa.2024.102509
Jacob A. Wolfe, W. Seth Horne
{"title":"Application of artificial backbone connectivity in the development of metalloenzyme mimics","authors":"Jacob A. Wolfe,&nbsp;W. Seth Horne","doi":"10.1016/j.cbpa.2024.102509","DOIUrl":"10.1016/j.cbpa.2024.102509","url":null,"abstract":"<div><p>Metal-dependent enzymes are abundant and vital catalytic agents in nature. The functional versatility of metalloenzymes has made them common targets for improvement by protein engineering as well as mimicry by <em>de novo</em> designed sequences. In both strategies, the incorporation of non-canonical cofactors and/or non-canonical side chains has proved a useful tool. Less explored—but similarly powerful—is the utilization of non-canonical covalent modifications to the polypeptide backbone itself. Such efforts can entail either introduction of limited artificial monomers in natural chains to produce heterogeneous backbones or construction of completely abiotic oligomers that adopt defined folds. Herein, we review recent research applying artificial protein-like backbones in the construction of metalloenzyme mimics, highlighting progress as well as open questions in this emerging field.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102509"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000851/pdfft?md5=7682c3330f9c6aad812ea489aee31afc&pid=1-s2.0-S1367593124000851-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887842","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 the design and optimization of artificial metalloenzymes 人工金属酶设计和优化的最新进展。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 DOI: 10.1016/j.cbpa.2024.102508
Iori Morita, Thomas R. Ward
{"title":"Recent advances in the design and optimization of artificial metalloenzymes","authors":"Iori Morita,&nbsp;Thomas R. Ward","doi":"10.1016/j.cbpa.2024.102508","DOIUrl":"10.1016/j.cbpa.2024.102508","url":null,"abstract":"<div><p>Embedding a catalytically competent transition metal into a protein scaffold affords an artificial metalloenzyme (ArM). Such hybrid catalysts display features that are reminiscent of both homogeneous and enzymatic catalysts. Pioneered by Whitesides and Kaiser in the late 1970s, this field of ArMs has expanded over the past two decades, marked by ever-increasing diversity in reaction types, cofactors, and protein scaffolds. Recent noteworthy developments include i) the use of earth-abundant metal cofactors, ii) concurrent cascade reactions, iii) synergistic catalysis, and iv) <em>in vivo</em> catalysis. Thanks to significant progress in computational protein design, ArMs based on <em>de novo</em>–designed proteins and tailored chimeric proteins promise a bright future for this exciting field.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102508"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887843","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
Glutathione dynamics in subcellular compartments and implications for drug development 亚细胞区室中的谷胱甘肽动态及其对药物开发的影响。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 DOI: 10.1016/j.cbpa.2024.102505
Hanfeng Lin , Lingfei Wang , Xiqian Jiang , Jin Wang
{"title":"Glutathione dynamics in subcellular compartments and implications for drug development","authors":"Hanfeng Lin ,&nbsp;Lingfei Wang ,&nbsp;Xiqian Jiang ,&nbsp;Jin Wang","doi":"10.1016/j.cbpa.2024.102505","DOIUrl":"10.1016/j.cbpa.2024.102505","url":null,"abstract":"<div><p>Glutathione (GSH) is a pivotal tripeptide antioxidant essential for maintaining cellular redox homeostasis and regulating diverse cellular processes. Subcellular compartmentalization of GSH underscores its multifaceted roles across various organelles including the cytosol, mitochondria, endoplasmic reticulum, and nucleus, each exhibiting distinct regulatory mechanisms. Perturbations in GSH dynamics contribute to pathophysiological conditions, emphasizing the clinical significance of understanding its intricate regulation. This review consolidates current knowledge on subcellular GSH dynamics, highlighting its implications in drug development, particularly in covalent drug design and antitumor strategies targeting intracellular GSH levels. Challenges and future directions in deciphering subcellular GSH dynamics are discussed, advocating for innovative methodologies to advance our comprehension and facilitate the development of precise therapeutic interventions based on GSH modulation.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102505"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756040","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
MicroRNA:Siglec crosstalk in cancer progression 微 RNA：Siglec 在癌症进展中的相互影响
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-07-18 DOI: 10.1016/j.cbpa.2024.102502
D. Mustafov , M.S. Ahmad , A. Serrano , M. Braoudaki , S.S. Siddiqui
{"title":"MicroRNA:Siglec crosstalk in cancer progression","authors":"D. Mustafov ,&nbsp;M.S. Ahmad ,&nbsp;A. Serrano ,&nbsp;M. Braoudaki ,&nbsp;S.S. Siddiqui","doi":"10.1016/j.cbpa.2024.102502","DOIUrl":"10.1016/j.cbpa.2024.102502","url":null,"abstract":"<div><p>Aberrant Siglec expression in the tumour microenvironment has been implicated in tumour malignancies and can impact tumour behaviour and patient survival. Further to this, engagement with sialoglycans induces masked antigen recognition and promotes immune evasion, highlighting deregulated immune function. This necessitates the elucidation of their expression profiles in tumour progression. MicroRNAs (miRNAs) mediated targeting represents a novel approach to further elucidate Siglec potential and clinical relevance. Although miRNA activity in Siglec expression remains limited, we highlight current literature detailing miRNA:Siglec interactions within the tumour landscape and provide insights for possible diagnostic and therapeutic strategies in targeting the Siglec/sialic acid axis.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102502"},"PeriodicalIF":6.9,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000784/pdfft?md5=fa5f5ed0a0c37a6bae4a3703795bb511&pid=1-s2.0-S1367593124000784-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637816","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 methods for quantifying the cell penetration of macromolecules 大分子细胞渗透量化方法的最新进展
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-07-17 DOI: 10.1016/j.cbpa.2024.102501
Nefeli Batistatou, Joshua A. Kritzer
{"title":"Recent advances in methods for quantifying the cell penetration of macromolecules","authors":"Nefeli Batistatou,&nbsp;Joshua A. Kritzer","doi":"10.1016/j.cbpa.2024.102501","DOIUrl":"10.1016/j.cbpa.2024.102501","url":null,"abstract":"<div><p>As the landscape of macromolecule therapeutics advances, drug developers are continuing to aim at intracellular targets. To activate, inhibit, or degrade these targets, the macromolecule must be delivered efficiently to intracellular compartments. Quite often, there is a discrepancy between binding affinity in biochemical assays and activity in cell-based assays. Identifying the bottleneck for cell-based activity requires robust assays that quantify total cellular uptake and/or cytosolic delivery. Recognizing this need, chemical biologists have designed a plethora of assays to make this measurement, each with distinct advantages and disadvantages. In this review, we describe the latest and most promising developments in the last 3 to 4 years.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102501"},"PeriodicalIF":6.9,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637815","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
Rational design of lipid nanoparticles: overcoming physiological barriers for selective intracellular mRNA delivery 合理设计脂质纳米颗粒：克服生理障碍，选择性地在细胞内输送 mRNA。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-07-13 DOI: 10.1016/j.cbpa.2024.102499
Yu Zhao , Zeyu Morgan Wang , Donghui Song , Mengting Chen, Qiaobing Xu
{"title":"Rational design of lipid nanoparticles: overcoming physiological barriers for selective intracellular mRNA delivery","authors":"Yu Zhao ,&nbsp;Zeyu Morgan Wang ,&nbsp;Donghui Song ,&nbsp;Mengting Chen,&nbsp;Qiaobing Xu","doi":"10.1016/j.cbpa.2024.102499","DOIUrl":"10.1016/j.cbpa.2024.102499","url":null,"abstract":"<div><p>This review introduces the typical delivery process of messenger RNA (mRNA) nanomedicines and concludes that the delivery involves a at least four-step <strong>SCER</strong> cascade and that high efficiency at every step is critical to guarantee high overall therapeutic outcomes. This <strong>SCER</strong> cascade process includes selective organ-targeting delivery, cellular uptake, endosomal escape, and cytosolic mRNA release. Lipid nanoparticles (LNPs) have emerged as a state-of-the-art vehicle for <em>in vivo</em> mRNA delivery. The review emphasizes the importance of LNPs in achieving selective, efficient, and safe mRNA delivery. The discussion then extends to the technical and clinical considerations of LNPs, detailing the roles of individual components in the SCER cascade process, especially ionizable lipids and helper phospholipids. The review aims to provide an updated overview of LNP-based mRNA delivery, outlining recent innovations and addressing challenges while exploring future developments for clinical translation over the next decade.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102499"},"PeriodicalIF":6.9,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597988","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 glycoengineering: Cell-based and cell-free routes for producing biopharmaceuticals with customized glycosylation 细菌糖工程：以细胞为基础和无细胞途径生产定制糖基化生物制药。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-07-10 DOI: 10.1016/j.cbpa.2024.102500
Jaymee A. Palma , Mehman I. Bunyatov , Sophia W. Hulbert , Michael C. Jewett , Matthew P. DeLisa
{"title":"Bacterial glycoengineering: Cell-based and cell-free routes for producing biopharmaceuticals with customized glycosylation","authors":"Jaymee A. Palma ,&nbsp;Mehman I. Bunyatov ,&nbsp;Sophia W. Hulbert ,&nbsp;Michael C. Jewett ,&nbsp;Matthew P. DeLisa","doi":"10.1016/j.cbpa.2024.102500","DOIUrl":"10.1016/j.cbpa.2024.102500","url":null,"abstract":"<div><p>Glycosylation plays a pivotal role in tuning the folding and function of proteins. Because most human therapeutic proteins are glycosylated, understanding and controlling glycosylation is important for the design, optimization, and manufacture of biopharmaceuticals. Unfortunately, natural eukaryotic glycosylation pathways are complex and often produce heterogeneous glycan patterns, making the production of glycoproteins with chemically precise and homogeneous glycan structures difficult. To overcome these limitations, bacterial glycoengineering has emerged as a simple, cost-effective, and scalable approach to produce designer glycoprotein therapeutics and vaccines in which the glycan structures are engineered to reduce heterogeneity and improve biological and biophysical attributes of the protein. Here, we discuss recent advances in bacterial cell-based and cell-free glycoengineering that have enabled the production of biopharmaceutical glycoproteins with customized glycan structures.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102500"},"PeriodicalIF":6.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589171","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
Advancements in boron difluoride formazanate dyes for biological imaging 用于生物成像的二氟化硼甲臢酸盐染料的研究进展。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-07-09 DOI: 10.1016/j.cbpa.2024.102473
Shudan Yang , Kang Lu , Han Xiao
{"title":"Advancements in boron difluoride formazanate dyes for biological imaging","authors":"Shudan Yang ,&nbsp;Kang Lu ,&nbsp;Han Xiao","doi":"10.1016/j.cbpa.2024.102473","DOIUrl":"10.1016/j.cbpa.2024.102473","url":null,"abstract":"<div><p>In the past decade, boron difluoride formazanate dyes have gained considerable attention due to their redox activity, high absorption and emission intensities, chemical stability across a broad range of conditions, and the ease to fine-tune their optical and electronic characteristics. Over the past five years, boron difluoride formazanate dyes have demonstrated their extended emission wavelengths in the near-infrared region, suggesting their potential applications in the field of biological imaging. This review provides an overview of the evolution of boron difluoride formazanate dyes, encompassing the structural variations and corresponding optical properties, while also highlighting their current applications in biological imaging fields.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102473"},"PeriodicalIF":6.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578463","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
Editorial overview: Recent advances in metabolomics 编辑综述：代谢组学的最新进展。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-07-08 DOI: 10.1016/j.cbpa.2024.102498
James S.O. McCullagh, Hector C. Keun
{"title":"Editorial overview: Recent advances in metabolomics","authors":"James S.O. McCullagh,&nbsp;Hector C. Keun","doi":"10.1016/j.cbpa.2024.102498","DOIUrl":"10.1016/j.cbpa.2024.102498","url":null,"abstract":"","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102498"},"PeriodicalIF":6.9,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562188","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 strides in macromolecular targeted photodynamic therapy for cancer 癌症大分子靶向光动力疗法的最新进展
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-07-05 DOI: 10.1016/j.cbpa.2024.102497
Maxwell B. Quaye, Girgis Obaid
{"title":"Recent strides in macromolecular targeted photodynamic therapy for cancer","authors":"Maxwell B. Quaye,&nbsp;Girgis Obaid","doi":"10.1016/j.cbpa.2024.102497","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102497","url":null,"abstract":"<div><p>The recent approval of Akalux® for antibody-targeted photodynamic therapy (PDT) in Japan (also known as photoimmunotherapy), and the recent approval of Cytalux® for folate-specific image guided surgery by the FDA have motivated the continued development of macromolecular targeted PDT for cancer management. This review spotlights some of the most recent advances in macromolecular targeted PDT since 2021, exploring the latest advances in protein engineering, adaptive macromolecular constructs and nanotechnology, adoption of immune checkpoint inhibitors, and targeting using biomimetic membranes. These strategies summarized here attempt to expand the functionality, benefit, and success of macromolecular targeting for PDT to advance the technology beyond what has already entered into the clinical realm.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102497"},"PeriodicalIF":6.9,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000735/pdfft?md5=abb39fc10d3de6fdc5c0ae66b349a979&pid=1-s2.0-S1367593124000735-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141543003","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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