Hanfeng Lin , Lingfei Wang , Xiqian Jiang , Jin Wang
{"title":"Glutathione dynamics in subcellular compartments and implications for drug development","authors":"Hanfeng Lin , Lingfei Wang , Xiqian Jiang , 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":null,"pages":null},"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}
D. Mustafov , M.S. Ahmad , A. Serrano , M. Braoudaki , S.S. Siddiqui
{"title":"MicroRNA:Siglec crosstalk in cancer progression","authors":"D. Mustafov , M.S. Ahmad , A. Serrano , M. Braoudaki , 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":null,"pages":null},"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}
{"title":"Recent advances in methods for quantifying the cell penetration of macromolecules","authors":"Nefeli Batistatou, 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":null,"pages":null},"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}
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 , Zeyu Morgan Wang , Donghui Song , Mengting Chen, 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":null,"pages":null},"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}
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 , Mehman I. Bunyatov , Sophia W. Hulbert , Michael C. Jewett , 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":null,"pages":null},"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}
{"title":"Advancements in boron difluoride formazanate dyes for biological imaging","authors":"Shudan Yang , Kang Lu , 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":null,"pages":null},"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}
{"title":"Editorial overview: Recent advances in metabolomics","authors":"James S.O. McCullagh, 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":null,"pages":null},"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}
{"title":"Recent strides in macromolecular targeted photodynamic therapy for cancer","authors":"Maxwell B. Quaye, 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":null,"pages":null},"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}
{"title":"Strategies in engineering sustainable biochemical synthesis through microbial systems","authors":"Yoseb Song, Kristala L.J. Prather","doi":"10.1016/j.cbpa.2024.102493","DOIUrl":"10.1016/j.cbpa.2024.102493","url":null,"abstract":"<div><p>Growing environmental concerns and the urgency to address climate change have increased demand for the development of sustainable alternatives to fossil-derived fuels and chemicals. Microbial systems, possessing inherent biosynthetic capabilities, present a promising approach for achieving this goal. This review discusses the coupling of systems and synthetic biology to enable the elucidation and manipulation of microbial phenotypes for the production of chemicals that can substitute for petroleum-derived counterparts and contribute to advancing green biotechnology. The integration of artificial intelligence with metabolic engineering to facilitate precise and data-driven design of biosynthetic pathways is also discussed, along with the identification of current limitations and proposition of strategies for optimizing biosystems, thereby propelling the field of chemical biology towards sustainable chemical production.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544254","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}
{"title":"How are hydrogen peroxide messages relayed to affect cell signalling?","authors":"Elizabeth A. Veal , Paraskevi Kritsiligkou","doi":"10.1016/j.cbpa.2024.102496","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102496","url":null,"abstract":"<div><p>H<sub>2</sub>O<sub>2</sub> signals trigger adaptive responses affecting cell division, differentiation, migration, and survival. These signals are transduced by selective oxidation of cysteines on specific target proteins, with redox-sensitive cysteines now identified in many proteins, including both kinases and phosphatases. Assessing the contribution of these oxidation events to cell signalling presents several challenges including understanding how and when the selective oxidation of specific proteins takes place <em>in vivo</em>. In recent years, a combination of biochemical, structural, genetic, and computational approaches in fungi, plants, and animals have revealed different ways in which thiol peroxidases (peroxiredoxins) are bypassed or utilised in relaying these signals. Together, these mechanisms provide a conceptual framework for selectively oxidising proteins that will further advance understanding of how redox modifications contribute to health and disease.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000723/pdfft?md5=0f60fd470519d7a47684751d6879061a&pid=1-s2.0-S1367593124000723-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141482246","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}