Israel Journal of Chemistry最新文献

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The Great Codon Escape: Vacating Codons for Genetic Code Expansion and Ribosome Stalling 密码子大逃亡空缺密码子促进遗传密码扩展和核糖体停滞
IF 2.3 4区 化学
Israel Journal of Chemistry Pub Date : 2024-06-12 DOI: 10.1002/ijch.202400012
Antonius J. P. Hopstaken, Enno Große Wichtrup, Dr. Seino A. K. Jongkees
{"title":"The Great Codon Escape: Vacating Codons for Genetic Code Expansion and Ribosome Stalling","authors":"Antonius J. P. Hopstaken,&nbsp;Enno Große Wichtrup,&nbsp;Dr. Seino A. K. Jongkees","doi":"10.1002/ijch.202400012","DOIUrl":"10.1002/ijch.202400012","url":null,"abstract":"<p>In ribosomal synthesis of peptides and proteins, genetic information is translated into an amino acid polymer according to the genetic code, which describes the translational command encoded by each codon. However, parts of the genetic code can be adjusted to customize translations. One option is to remove decoding for a specific codon, resulting in a vacant codon. Such vacant codons can be used to stall the ribosome for mechanistic studies and display techniques. Alternatively, the liberated codon can be assigned to encode for incorporation of a noncanonical building block for expansion of the genetic code. In this review we provide an overview of the methods currently available for vacating codons in prokaryotic translation (agnostic of how these are later applied), targeting factors such as amino-acyl tRNA synthetases, tRNA, release factors, and the initiation machinery. Moreover, we assess applicability and compatibility of the currently available techniques and discuss which have the potential to develop into even more powerful approaches in the future.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 8-9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202400012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141352039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Supramolecular Approaches to the Detoxification of Nerve Agents 神经毒剂的超分子解毒方法
IF 2.3 4区 化学
Israel Journal of Chemistry Pub Date : 2024-06-11 DOI: 10.1002/ijch.202400019
Prof. Dr. Stefan Kubik
{"title":"Supramolecular Approaches to the Detoxification of Nerve Agents","authors":"Prof. Dr. Stefan Kubik","doi":"10.1002/ijch.202400019","DOIUrl":"10.1002/ijch.202400019","url":null,"abstract":"<p>A promising, but not yet practiced, approach to the treatment of neurotoxic organophosphate poisoning is the administration of a scavenger that rapidly deactivates the nerve agent before it can exert its toxic effects. The detoxification rates required for successful use of this therapy can currently only be achieved with enzymes, but synthetic scavengers, whose mode of action is based on key concepts of supramolecular chemistry, are an attractive alternative. Considerable progress has recently been made in the development of such scavengers, and compounds from several receptor classes are now available that not only bind nerve agents but also degrade them at promising rates. This review provides an overview of the field and highlights recent developments.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 6-7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202400019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141357892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Properties of the Ammann–Beenker Tiling and its Square Periodic Approximants 安曼-贝克尔平铺及其平方周期近似值的特性
IF 2.3 4区 化学
Israel Journal of Chemistry Pub Date : 2024-06-04 DOI: 10.1002/ijch.202300119
Anuradha Jagannathan, Michel Duneau
{"title":"Properties of the Ammann–Beenker Tiling and its Square Periodic Approximants","authors":"Anuradha Jagannathan,&nbsp;Michel Duneau","doi":"10.1002/ijch.202300119","DOIUrl":"https://doi.org/10.1002/ijch.202300119","url":null,"abstract":"<p>Our understanding of physical properties of quasicrystals owes a great deal to studies of tight-binding models constructed on quasiperiodic tilings. Among the large number of possible quasiperiodic structures, two dimensional tilings are of particular importance – in their own right, but also for information regarding properties of three dimensional systems. We provide here a users manual for those wishing to construct and study physical properties of the 8-fold Ammann–Beenker quasicrystal, a good starting point for investigations of two dimensional quasiperiodic systems. This tiling has a relatively straightforward construction. Thus, geometrical properties such as the type and number of local environments can be readily found by simple analytical computations. Transformations of sites under discrete scale changes – called inflations and deflations – are easier to establish compared to the celebrated Penrose tiling, for example. We have aimed to describe the methodology with a minimum of technicalities but in sufficient detail so as to enable non-specialists to generate quasiperiodic tilings and periodic approximants, with or without disorder. The discussion of properties includes some relations not previously published, and examples with figures.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142860073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spatially and Single-Cell Resolved Profiling of RNA Life Cycle and Epitranscriptomics 以空间和单细胞分辨率剖析 RNA 生命周期和外显子转录组学
IF 2.3 4区 化学
Israel Journal of Chemistry Pub Date : 2024-06-03 DOI: 10.1002/ijch.202400028
Qiyang Zhou, Jianting Guo, Xiao Wang
{"title":"Spatially and Single-Cell Resolved Profiling of RNA Life Cycle and Epitranscriptomics","authors":"Qiyang Zhou,&nbsp;Jianting Guo,&nbsp;Xiao Wang","doi":"10.1002/ijch.202400028","DOIUrl":"10.1002/ijch.202400028","url":null,"abstract":"<p>The intricate network of cell functions relies on gene expression programs, where the whole RNA life cycle from DNA to protein is subjected to extensive transcriptional and post-transcriptional gene regulation events. Established bulk RNA sequencing methods provide an averaged, transcriptome-wide quantification of the RNA life cycle, including transcription, processing, translation, transport, and degradation through RNA-protein interactions. Furthermore, numerous studies using bulk epitranscriptomic profiling unveiled that dynamic RNA modifications (e. g., <i>N</i><sup>6</sup>-Methyladenosine), add another layer of gene regulations. However, many regulatory events are cell-type specific, subcellularly localized, and subjected to cell-cell communications within the native tissue environment. Thanks to the advances in single-cell sequencing, spatial sequencing, and highly multiplexed imaging methods, we can routinely measure single-cell and spatial transcriptomics. Yet more comprehensive methods to profile every step of the RNA life cycle with single-cell and spatial information are still lacking. In this review, we will summarize and compare early explorations in developing state-of-the-art methods for spatially and single-cell resolved mapping of RNA kinetics, translation, RNA-protein interactions, and epitranscriptomics. It is promising that these new techniques will greatly facilitate our understanding of the RNA-centered regulation landscapes in different cell types and how the post-transcriptional regulations are interconnected within cellular and tissue architecture.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 5","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202400028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141270198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Direct, Quantitative, and Base-Resolution Sequencing of DNA and RNA Modifications 对 DNA 和 RNA 修饰进行直接、定量和碱基分辨率测序
IF 2.3 4区 化学
Israel Journal of Chemistry Pub Date : 2024-05-31 DOI: 10.1002/ijch.202400007
Haiqi Xu, Chun-Xiao Song
{"title":"Direct, Quantitative, and Base-Resolution Sequencing of DNA and RNA Modifications","authors":"Haiqi Xu,&nbsp;Chun-Xiao Song","doi":"10.1002/ijch.202400007","DOIUrl":"10.1002/ijch.202400007","url":null,"abstract":"<p>Cellular DNA and RNA are decorated with diverse chemical modifications, which add new layers to gene regulation and play crucial roles across development and disease progression. Interest in understanding the functions of DNA and RNA modifications, as well as the related molecular mechanisms, has been growing, driving progress in developing chemical and biochemical tools to detect specific modifications. New technologies are important not only for uncovering biological functions, but also for driving conceptual revolutions. In this review, we highlighted our recent advances in developing new chemical tools to detect DNA and RNA modifications in a direct, quantitative, and base-resolution manner. These includes a novel borane reduction chemistry for DNA methylation sequencing; new cytosine modificaiton oxdation chemistry for enhanced DNA hydroxymethylation sequencing; and a novel bromoacrylamide cyclization chemistry for RNA pseudouridylation sequencing. We present a mechanistic overview of these tools and their applications in epigenetic and epitranscriptomic research.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 5","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202400007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141197612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ethnic Variation and Structure‐Function Analysis of Tauopathy‐Associated PERK Alleles 与 Tauopathy 相关的 PERK 等位基因的种族差异和结构功能分析
IF 3.2 4区 化学
Israel Journal of Chemistry Pub Date : 2024-05-24 DOI: 10.1002/ijch.202300173
Goonho Park, Angela Galdamez, Keon‐Hyoung Song, Masako Le, Kyle Kim, Jonathan H. Lin
{"title":"Ethnic Variation and Structure‐Function Analysis of Tauopathy‐Associated PERK Alleles","authors":"Goonho Park, Angela Galdamez, Keon‐Hyoung Song, Masako Le, Kyle Kim, Jonathan H. Lin","doi":"10.1002/ijch.202300173","DOIUrl":"https://doi.org/10.1002/ijch.202300173","url":null,"abstract":"EIF2AK3, also known as PERK, plays a pivotal role in cellular proteostasis, orchestrating the Unfolded Protein Response (UPR) and Integrated Stress Response (ISR) pathways. In addition to its central position in intracellular stress regulation, human GWAS identify EIF2AK3 as a risk factor in tauopathies, neurodegenerative diseases caused by aberrant tau protein accumulation. Guided by these genomic indicators, our investigation systematically analyzed human PERK variants, focusing on those with potential tauopathy linkages. We assembled a comprehensive data set of human PERK variants associated with Wolcott Rallison Syndrome (WRS), tauopathies, and bioinformatically predicted loss‐of‐function, referencing the gnomAD, Ensembl, and NCBI databases. We found extensive racial/ethnic variation in the prevalence of common <jats:italic>PERK</jats:italic> polymorphisms linked to tauopathies. Using SWISS‐MODEL, we identified structural perturbations in the ER stress‐sensing luminal domain dimers/oligomers of tauopathy‐associated PERK variants, Haplotypes A and B, in combination with another tauopathy‐linked R240H mutation. Recombinant expression of disease‐associated variants <jats:italic>in vitro</jats:italic> revealed altered PERK signal transduction kinetics in response to ER stress compared to the predominant non‐disease variant. In summary, our data further substantiates that human PERK variants identified in tauopathy genetic studies negatively impact PERK structure, function, and downstream signaling with significant variations in prevalence among different racial and ethnic groups.","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"35 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Porous Crystalline Organic Cages Made by Design 设计制造的多孔结晶有机笼
IF 2.3 4区 化学
Israel Journal of Chemistry Pub Date : 2024-05-15 DOI: 10.1002/ijch.202400025
Dr. Svetlana Ivanova, Prof. Dr. Florian Beuerle
{"title":"Porous Crystalline Organic Cages Made by Design","authors":"Dr. Svetlana Ivanova,&nbsp;Prof. Dr. Florian Beuerle","doi":"10.1002/ijch.202400025","DOIUrl":"10.1002/ijch.202400025","url":null,"abstract":"<p>Shape-persistent organic cages are an intriguing class of molecular porous materials. Through hierarchical molecular design, size and shape of the intrinsic molecular voids are controlled by dynamic covalent chemistry, while pore structure and topology are governed by noncovalent alignment in the solid state. However, the predictable and reliable crystallization of organic cages is still challenging since long-range superstructures are solely based on weak and rather unidirectional supramolecular interactions. In this tutorial review, we provide a general classification of porous solid-state materials and discuss specific design principles regarding the dynamic covalent reactions, the small-molecule building blocks and solid-state engineering. Furthermore, we introduce the most important analytical techniques for porous materials with a special focus on organic cages.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 6-7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202400025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140973743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cytokine Mimetics with Various Modalities 各种模式的细胞因子模拟物
IF 2.3 4区 化学
Israel Journal of Chemistry Pub Date : 2024-05-14 DOI: 10.1002/ijch.202300163
Katsuya Sakai, Hiroki Sato, Kunio Matsumoto
{"title":"Cytokine Mimetics with Various Modalities","authors":"Katsuya Sakai,&nbsp;Hiroki Sato,&nbsp;Kunio Matsumoto","doi":"10.1002/ijch.202300163","DOIUrl":"10.1002/ijch.202300163","url":null,"abstract":"<p>Cytokines play a central role in regulating cell communication and signal transduction, since they influence processes such as immunity, hematopoiesis, inflammatory disease, cancer, neurological disorders, and tissue healing. Notably, certain cytokines have been used clinically as protein therapeutics for conditions such as cancer, autoimmune diseases, and viral infections. Despite their therapeutic potential, cytokines often pose challenges, including side effects, stability constraints, and suboptimal pharmacokinetics. To address these limitations, there is growing interest in using diverse modalities to develop alternative cytokines with enhanced properties and therapeutic benefits. Of these modalities, effective high-throughput screening of macrocyclic peptides enabled by RNA-based catalysis has emerged as a promising candidate method for the development of alternative cytokines. Here, we focus on the development of cytokine alternatives using various approaches and explore prospects for their future use as therapeutic agents.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 8-9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140980242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Display Technologies for Expanding the Pharmaceutical Applications of Cyclotides 拓展环苷酸药物应用的显示技术
IF 2.3 4区 化学
Israel Journal of Chemistry Pub Date : 2024-05-06 DOI: 10.1002/ijch.202400010
Jing Xie, Meng-Wei Kan, Simon J. de Veer, Conan Wang, David J. Craik
{"title":"Display Technologies for Expanding the Pharmaceutical Applications of Cyclotides","authors":"Jing Xie,&nbsp;Meng-Wei Kan,&nbsp;Simon J. de Veer,&nbsp;Conan Wang,&nbsp;David J. Craik","doi":"10.1002/ijch.202400010","DOIUrl":"10.1002/ijch.202400010","url":null,"abstract":"<p>Cyclotides are ultra-stable peptides originally discovered in plants based on their medicinal applications. Their natural function is as host defence agents. They are amenable to chemical synthesis for use as scaffolds for drug design applications. Cyclotides comprise ~30 amino acids and in addition to having a head-to-tail cyclic backbone, incorporate six conserved cystine residues connected in a cystine knot motif. The cyclic backbone and cystine knot contribute to their exceptional resistance to proteases or thermal denaturation, making them useful scaffolds for drug design applications. The backbone segments, or loops, between the conserved cysteine residues are amenable to combinatorial variation in native cyclotides and have also been used to incorporate selected bioactive peptide epitopes into a range of synthetic cyclotides and cyclotide-like scaffolds. In the past this was largely done via low throughput structure-based design approaches, but the discovery of novel cyclotide binders has been greatly enhanced by the use of combinatorial display approaches on cyclotide scaffolds using phage, bacterial, yeast and mRNA technologies, as reviewed herein.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 8-9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202400010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140883251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Strategies for Detecting Aminoacylation and Aminoacyl-tRNA Editing in vitro and in Cells 体外和细胞内检测氨基酰化和氨基酰-tRNA 编辑的策略
IF 2.3 4区 化学
Israel Journal of Chemistry Pub Date : 2024-05-06 DOI: 10.1002/ijch.202400009
Rylan R. Watkins, Arundhati Kavoor, Prof. Karin Musier-Forsyth
{"title":"Strategies for Detecting Aminoacylation and Aminoacyl-tRNA Editing in vitro and in Cells","authors":"Rylan R. Watkins,&nbsp;Arundhati Kavoor,&nbsp;Prof. Karin Musier-Forsyth","doi":"10.1002/ijch.202400009","DOIUrl":"10.1002/ijch.202400009","url":null,"abstract":"<p>Aminoacyl-tRNA synthetases (aaRSs) maintain translational fidelity by ensuring the formation of correct aminoacyl-tRNA pairs. Numerous point mutations in human aaRSs have been linked to disease phenotypes. Structural studies of aaRSs from human pathogens encoding unique domains support these enzymes as potential candidates for therapeutics. Studies have shown that the identity of tRNA pools in cells changes between different cell types and under stress conditions. While traditional radioactive aminoacylation analyses can determine the effect of disease-causing mutations on aaRS function, these assays are not amenable to drug discovery campaigns and do not take into account the variability of the intracellular tRNA pools. Here, we review modern techniques to characterize aaRS activity <i>in vitro</i> and in cells. The cell-based approaches analyse the aminoacyl-tRNA pool to observe trends in aaRS activity and fidelity. Taken together, these approaches allow high-throughput drug screening of aaRS inhibitors and systems-level analyses of the dynamic tRNA population under a variety of conditions and disease states.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 8-9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202400009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140883430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","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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