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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 : 2024-08-01 Epub 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":"2024-08-01","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
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 : 2024-08-01 Epub 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":"2024-08-01","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
New reactions by pyridoxal phosphate-dependent enzymes 依赖磷酸吡哆醛的酶的新反应
IF 7.8 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-05-29 DOI: 10.1016/j.cbpa.2024.102472
Phillip Daniel-Ivad, Katherine S. Ryan
{"title":"New reactions by pyridoxal phosphate-dependent enzymes","authors":"Phillip Daniel-Ivad,&nbsp;Katherine S. Ryan","doi":"10.1016/j.cbpa.2024.102472","DOIUrl":"10.1016/j.cbpa.2024.102472","url":null,"abstract":"<div><p>Pyridoxal phosphate (PLP) is a cofactor that is widely employed in enzymology. This pyridine-containing cofactor can be used for reactions ranging from transaminations to oxidations. The catalytic versatility can be understood by considering the chemical features of this cofactor. In recent years, exciting new reactions involving PLP have been discovered in natural products biosynthesis, upending our understanding of what this cofactor is capable of. Here we review some of the most exciting PLP-dependent reactions from the last five years.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102472"},"PeriodicalIF":7.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000486/pdfft?md5=90c95973227f092b2660e8c5a58d3bd9&pid=1-s2.0-S1367593124000486-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178450","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
Biosynthesis and recruitment of reactive amino acids in nonribosomal peptide assembly lines 非核糖体肽组装线中活性氨基酸的生物合成和招募。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-06-26 DOI: 10.1016/j.cbpa.2024.102494
Friedrich Johannes Ehinger , Christian Hertweck
{"title":"Biosynthesis and recruitment of reactive amino acids in nonribosomal peptide assembly lines","authors":"Friedrich Johannes Ehinger ,&nbsp;Christian Hertweck","doi":"10.1016/j.cbpa.2024.102494","DOIUrl":"10.1016/j.cbpa.2024.102494","url":null,"abstract":"<div><p>Reactive amino acid side chains play important roles in the binding of peptides to specific targets. In addition, their reactivity enables selective peptide conjugation and functionalization for pharmaceutical purposes. Diverse reactive amino acids are incorporated into nonribosomal peptides, which serve as a source for drug candidates. Notable examples include (poly)unsaturated (enamine, alkyne, and furyl) and halogenated residues, strained carbacycles (cyclopropyl and cyclopropanol), small heterocycles (oxirane and aziridine), and reactive N–N functionalities (hydrazones, diazo compounds, and diazeniumdiolates). Their biosynthesis requires diverse biocatalysts for sophisticated reaction mechanisms. Several avenues have been identified for their incorporation into peptides, the recruitment by adenylation domains or ligases, on-line modifications, and enzymatic tailoring reactions. Combined with protein engineering approaches, this knowledge provides new opportunities in synthetic biology and bioorthogonal chemistry.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102494"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464805","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 applications of fluorescence correlation spectroscopy in live cells 荧光相关光谱在活细胞中的最新应用
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-06-20 DOI: 10.1016/j.cbpa.2024.102480
Adam W. Smith
{"title":"Recent applications of fluorescence correlation spectroscopy in live cells","authors":"Adam W. Smith","doi":"10.1016/j.cbpa.2024.102480","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102480","url":null,"abstract":"<div><p>As a time-domain analogue of fluorescence imaging, FCS offers valuable insights into molecular dynamics, interactions, and concentrations within living cells. The primary insight generated by FCS is molecular mobility and concentration, which makes it useful for investigating molecular-scale details without the need for enrichment or separation. A specific strength of FCS is the ability to probe protein–protein interactions in live cells and several recent applications in this area are summarized. FCS is also used to investigate plasma membrane protein organization, with many applications to cell surface receptors and the mechanisms of drug binding. Finally, FCS is undergoing continual methodological innovations, such as imaging FCS, SPIM-FCS PIE-FCCS, STED-FCS, three-color FCS, and massively parallel FCS, which extend the capabilities to investigate molecular dynamics at different spatial and temporal scales. These innovations enable detailed examinations of cellular processes, including cellular transport and the spatial organization of membrane proteins.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102480"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434922","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 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 : 2024-08-01 Epub 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":"2024-08-01","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
Reactions of lipid hydroperoxides and how they may contribute to ferroptosis sensitivity 脂质氢过氧化物的反应及其对铁中毒敏感性的影响
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-06-21 DOI: 10.1016/j.cbpa.2024.102478
Dmitry D. Saraev, Derek A. Pratt
{"title":"Reactions of lipid hydroperoxides and how they may contribute to ferroptosis sensitivity","authors":"Dmitry D. Saraev,&nbsp;Derek A. Pratt","doi":"10.1016/j.cbpa.2024.102478","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102478","url":null,"abstract":"<div><p>The accumulation of lipid hydroperoxides (LOOHs) has long been associated with numerous pathologies and has more recently been shown to drive a specific type of cell death known as ferroptosis. In competition with their detoxification by glutathione peroxidases, LOOHs can react with both one-electron reductants and one-electron oxidants to afford radicals that initiate lipid peroxidation (LPO) chain reactions leading to more LOOH. These radicals can alternatively undergo a variety of (primarily unimolecular) reactions leading to electrophilic species that destabilize the membrane and/or react with cellular nucleophiles. While some reaction mechanisms leading to lipid-derived electrophiles have been known for some time, others have only recently been elucidated. Since LOOH (and related peroxides, LOOL) undergo these various reactions at different rates to afford distinct product distributions specific to their structures, not all LOOHs (and LOOLs) should be equivalently problematic for the cell – be it in their propensity to initiate further LPO or fragment to electrophiles, drive membrane permeabilization and eventual cell death. Herein we briefly review the fates of LOOH and discuss how they may contribute to the modulation of cell sensitivity to ferroptosis by different lipids.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102478"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000541/pdfft?md5=ce43e60434833511550b3e2a240cf1ab&pid=1-s2.0-S1367593124000541-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438050","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
The non-catalytic domains of O-GlcNAc cycling enzymes present new opportunities for function-specific control O-GlcNAc 循环酶的非催化结构域为特异性功能控制提供了新机遇
IF 7.8 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-06-10 DOI: 10.1016/j.cbpa.2024.102476
Chia-Wei Hu, Ke Wang, Jiaoyang Jiang
{"title":"The non-catalytic domains of O-GlcNAc cycling enzymes present new opportunities for function-specific control","authors":"Chia-Wei Hu,&nbsp;Ke Wang,&nbsp;Jiaoyang Jiang","doi":"10.1016/j.cbpa.2024.102476","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102476","url":null,"abstract":"<div><p>O-GlcNAcylation is an essential protein glycosylation governed by two O-GlcNAc cycling enzymes: O-GlcNAc transferase (OGT) installs a single sugar moiety <em>N-</em>acetylglucosamine (GlcNAc) on protein serine and threonine residues, and O-GlcNAcase (OGA) removes them. Aberrant O-GlcNAcylation has been implicated in various diseases. However, the large repertoire of more than 1000 O-GlcNAcylated proteins and the elusive mechanisms of OGT/OGA in substrate recognition present significant challenges in targeting the dysregulated O-GlcNAcylation for therapeutic development. Recently, emerging evidence suggested that the non-catalytic domains play critical roles in regulating the functional specificity of OGT/OGA via modulating their protein interactions and substrate recognition. Here, we discuss recent studies on the structures, mechanisms, and related tools of the OGT/OGA non-catalytic domains, highlighting new opportunities for function-specific control.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102476"},"PeriodicalIF":7.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302468","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
Enzymatic strategies for selenium incorporation into biological molecules 将硒纳入生物分子的酶促策略
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-07-01 DOI: 10.1016/j.cbpa.2024.102495
Chase M. Kayrouz , Mohammad R. Seyedsayamdost
{"title":"Enzymatic strategies for selenium incorporation into biological molecules","authors":"Chase M. Kayrouz ,&nbsp;Mohammad R. Seyedsayamdost","doi":"10.1016/j.cbpa.2024.102495","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102495","url":null,"abstract":"<div><p>The trace element selenium (Se) is essential to the physiology of most organisms on the planet. The most well documented of Se's biological forms are selenoproteins, where selenocysteine often serves as the catalytic center for crucial redox processes. Se is also found in several other classes of biological molecules, including nucleic acids, sugars, and modified amino acids, although its role in the function of these metabolites is less understood. Despite its prevalence, only a small number of Se-specific biosynthetic pathways have been discovered. Around half of these were first characterized in the past three years, suggesting that the selenometabolome may be more diverse than previously appreciated. Here, we review the recent advances in our understanding of this intriguing biochemical space, and discuss prospects for future discovery efforts.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102495"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141482220","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 in engineering sustainable biochemical synthesis through microbial systems 通过微生物系统进行可持续生化合成的工程战略。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.1016/j.cbpa.2024.102493
Yoseb Song, Kristala L.J. Prather
{"title":"Strategies in engineering sustainable biochemical synthesis through microbial systems","authors":"Yoseb Song,&nbsp;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":"81 ","pages":"Article 102493"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","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}
引用次数: 0
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