Israel Journal of Chemistry最新文献

{"title":"The 4th Bowei Research Conference (BRC-4), January 3–5, 2024, Teachers′ Hostel, Sun Moon Lake, Taiwan","authors":"Ehud Keinan","doi":"10.1002/ijch.202400018","DOIUrl":"10.1002/ijch.202400018","url":null,"abstract":"<p>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 1-2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202400018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139954867","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}

{"title":"Engineered RNA-Binding Proteins: Studying and Controlling RNA Regulation","authors":"Riley W. Sinnott,&nbsp;Yang Cao,&nbsp;Bryan C. Dickinson","doi":"10.1002/ijch.202300169","DOIUrl":"10.1002/ijch.202300169","url":null,"abstract":"<p>The complexity of eukaryotic organisms is intricately tied to transcriptome-level processes, notably alternative splicing and the precise modulation of gene expression through a sophisticated interplay involving RNA-binding protein (RBP) networks and their RNA targets. Recent advances in our understanding of the molecular pathways responsible for this control have paved the way for the development of tools capable of steering and managing RNA regulation and gene expression. The fusion between a rapidly developing understanding of endogenous RNA regulation and the burgeoning capabilities of CRISPR-Cas and other programmable RBP platforms has given rise to an exciting frontier in engineered RNA regulators. This review offers an overview of the existing toolkit for constructing synthetic RNA regulators using programmable RBPs and effector domains, capable of altering RNA sequence composition or fate, and explores their diverse applications in both basic research and therapeutic contexts.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 3-4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139927994","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}

{"title":"Structure-Activity Relationships of 2-(Arylthio)benzoic Acid FTO Inhibitors","authors":"Chao Yan,&nbsp;Qian Zhang,&nbsp;Pan Xiao,&nbsp;Xinyun Xie,&nbsp;Ming Li,&nbsp;Yuanlai Qiu,&nbsp;Liufa Wen,&nbsp;Xiaomin Song,&nbsp;Ze Dong,&nbsp;Cai-Guang Yang","doi":"10.1002/ijch.202300166","DOIUrl":"10.1002/ijch.202300166","url":null,"abstract":"<p>The biological role of the fat mass and obesity-associated protein (FTO) in the initiation and progress of acute myeloid leukemia (AML) has been elucidated, and several representative FTO inhibitors can markedly suppress the proliferation of AML cells. We previously developed FTO inhibitors including FB23. In this study, we adopted bioisosteric replacement of the intramolecular hydrogen bond in FB23 with a sulfur-oxygen interaction to generate a series of 2-(arylthio)benzoic acid FTO inhibitors and established their structure-activity relationships. Compound <b>8c</b> was the most potent 2-(arylthio)benzoic acid FTO inhibitor with an IC₅₀ value of 0.3±0.1 μM, which was comparable with that of FB23 <i>in vitro</i>. To enhance the antiproliferative effects in AML cell lines, we applied a prodrug strategy and prepared some esters. <b>7l</b>, the methyl ester of <b>8l</b>, exerted a superior inhibitory effect on a panel of AML cancer cell lines. Additionally, <b>7l</b> treatment notably increased global m⁶A abundance in AML cells. Collectively, our data suggest that 2-(arylthio)benzoic acid may be a new lead compound for inhibition of FTO, and the prodrug analog exhibit potential in the treatment of AML.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 3-4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139771114","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}

{"title":"Recent Advance in the Study on 5-Formylcytosine (f5C) RNA Modification","authors":"Xin Wang,&nbsp;Dr. Xiao-Yang Jin,&nbsp;Prof. Dr. Liang Cheng","doi":"10.1002/ijch.202300178","DOIUrl":"10.1002/ijch.202300178","url":null,"abstract":"<p>The widespread involvement of 5-formylcytosine f⁵C RNA in gene function regulation and its impact on crucial life processes like cell differentiation, embryonic development, and disease development underscores the significance of detecting this specific base modification. This detection holds great importance for basic epigenetics research and the early diagnosis and pathogenesis research of various diseases. This review aims to summarize recent research progress in f⁵C detection methods using selective chemical labeling, with the hope of aiding future research endeavors.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 3-4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770938","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}

{"title":"Protein Glycosylation Patterns Shaped By the IRE1-XBP1s Arm of the Unfolded Protein Response","authors":"Kenny Chen, Matthew D. Shoulders","doi":"10.1002/ijch.202300162","DOIUrl":"https://doi.org/10.1002/ijch.202300162","url":null,"abstract":"&lt;h2&gt; Protein Glycosylation&lt;/h2&gt;\u0000&lt;p&gt;Protein post-translational modifications, including phosphorylation, acetylation, ubiquitylation, and more, confer key levels of regulation and can dramatically alter the structure and function of proteins, acting as molecular switches or rheostats for tuning activity.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Many post-translational modifications are specialized to specific subcellular compartments and clientele, such as the sophisticated pathways for protein &lt;i&gt;N-&lt;/i&gt;glycosylation in the endoplasmic reticulum (ER) and Golgi mediated by a suite of glycosyltransferase and glycosidase enzymes. Protein glycosylation involves covalent modification of amino acid sidechains with sugars to yield linear or branched structures (glycans; Figure 1). The consequences of glycosylation shape protein function, cell–cell recognition, cell–matrix interactions, and more.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;\u0000&lt;/p&gt;\u0000&lt;figure&gt;&lt;picture&gt;\u0000&lt;source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/42668d07-8a7d-4cdf-b366-41629a41fe4c/ijch202300162-fig-0001-m.jpg\"/&gt;&lt;img alt=\"Details are in the caption following the image\" data-lg-src=\"/cms/asset/42668d07-8a7d-4cdf-b366-41629a41fe4c/ijch202300162-fig-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/821703d3-642e-4abd-a95c-a22057767b00/ijch202300162-fig-0001-m.png\" title=\"Details are in the caption following the image\"/&gt;&lt;/picture&gt;&lt;figcaption&gt;\u0000&lt;div&gt;&lt;strong&gt;Figure 1&lt;span style=\"font-weight:normal\"&gt;&lt;/span&gt;&lt;/strong&gt;&lt;div&gt;Open in figure viewer&lt;i aria-hidden=\"true\"&gt;&lt;/i&gt;&lt;span&gt;PowerPoint&lt;/span&gt;&lt;/div&gt;\u0000&lt;/div&gt;\u0000&lt;div&gt;\u0000&lt;p&gt;Protein &lt;i&gt;N&lt;/i&gt;-linked glycosylation is a co- and post-translational modification that involves the installation of glycans on asparagine side chains in specific amino acid sequons in proteins traversing the secretory pathway. &lt;i&gt;A&lt;/i&gt;: A 14-residue precursor oligosaccharide is first synthesized in a step-wise fashion while attached to a dolichol pyrophosphate molecule on the ER membrane. Monosaccharide substrates in the form of nucleotide sugars are each added to the growing sugar chain by their respective transferase enzymes. The dolichol-linked precursor then requires the action of flippase enzymes, prior to being added to a nascent ER client protein by the oligosaccharyltransferase (OST) complex as the polypeptide translocates from the ribosome to the ER. Note that &lt;i&gt;N&lt;/i&gt;-glycans can also be installed post-translationally by OST. After installation of the precursor, folding and initial trimming occurs in the ER and the nascent glycoprotein is trafficked to the Golgi for further processing. &lt;i&gt;B&lt;/i&gt;: Glycan-modifying enzymes in the ER and Golgi process the &lt;i&gt;N&lt;/i&gt;-glycan via sequential removal and addition of monosaccharides by specific enzymes, ultimately yielding a vast array of potential glycan structures, including hybrid glycans, complex glycans, core fucosylated glycans, and sialylated glycans. The specific identity of the glycan has important and varied consequences for cellular communication and the function of ","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"94 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139771087","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}

{"title":"Ising Spins on Frustrated Bronze-Mean Hexagonal Quasicrystal","authors":"Pratyay Ghosh","doi":"10.1002/ijch.202300113","DOIUrl":"https://doi.org/10.1002/ijch.202300113","url":null,"abstract":"<p>We investigate the Ising model on the Bronze-mean hexagonal quasicrystal (BMH QC), an aperiodic tiling with geometric frustration. Our extensive Monte Carlo simulations explore the model's rich phase diagram, revealing six distinct phases with diverse magnetic properties and degrees of frustration. We uncover exotic spin glass phases, signaled by the replica symmetry breaking and slow relaxation dynamics. We shed light on the intriguing magnetic properties of frustrated quasicrystals and open new avenues for studying exotic phases in condensed matter physics.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862294","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}

{"title":"Nanopore Direct RNA Sequencing for Modified Uridine Nucleotides Yields Signals Dependent on the Physical Properties of the Modified Base","authors":"Prof. Aaron M. Fleming,&nbsp;Justin C. Dingman,&nbsp;Yizhou Wu,&nbsp;Spencer S. Hoon,&nbsp;Prof. Cynthia J. Burrows","doi":"10.1002/ijch.202300177","DOIUrl":"10.1002/ijch.202300177","url":null,"abstract":"<p>Sequencing for RNA modifications with the nanopore direct RNA sequencing platform provides ionic current levels, helicase dwell times, and base call data that differentiate the modifications from the canonical form. Herein, model RNAs were synthesized with site-specific uridine (U) base modifications that enable the study of increasing an alkyl group size, halogen identity, or a change in base acidity to impact the nanopore data. The analysis concluded that increases in alkyl size trend with greater current blockage but a similar change in base-call error was not found. The addition of a halogen series to C5 of U revealed that the current levels recorded a trend with the water-octanol partition coefficient of the base, as well as the base call error. Studies with U modifications that are deprotonated (i. e., anionic) under the sequencing conditions gave broad current levels that influenced the base call error. Some modifications led to helicase dwell time changes. These insights provide design parameters for modification-specific chemical reagents that can shift nanopore signatures to minimize false positive reads, a known issue with this sequencing approach.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 3-4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581993","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}

{"title":"Pathogenicity Prediction of GABAA Receptor Missense Variants","authors":"Ya-Juan Wang, Giang H. Vu, Ting-Wei Mu","doi":"10.1002/ijch.202300161","DOIUrl":"https://doi.org/10.1002/ijch.202300161","url":null,"abstract":"&lt;h2&gt; Introduction&lt;/h2&gt;\u0000&lt;p&gt;Epilepsy is one of the most common neurological diseases in the world with a broad phenotypic spectrum.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Recent advances in genome sequencing identified an increasing number of genes that are associated with epilepsy.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; According to protein functions, epilepsy-associated genes can be grouped to ion channels, enzymes and enzyme modulators, transports and receptors, and others.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Genetic epilepsy is often linked to developmental delay, movement disorder, and other comorbidities.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Due to the important role of neurotransmitter-gated ion channels in controlling the excitation-inhibition balance in the central nervous system, genes encoding these ion channels, including excitatory N-methyl-D-aspartate (NMDA) receptors and inhibitory γ-aminobutyric acid type A (GABA&lt;sub&gt;A&lt;/sub&gt;) receptors, are recognized as prominent epilepsy-causing genes.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Here, we focus on GABA&lt;sub&gt;A&lt;/sub&gt; receptors, the primary inhibitory neurotransmitter-gated ion channels in the human brain.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; They mediate the fast inhibitory GABA-induced chloride currents and hyperpolarize the postsynaptic membranes to reduce neuronal firing.&lt;/p&gt;\u0000&lt;p&gt;Proteostasis maintenance of GABA&lt;sub&gt;A&lt;/sub&gt; receptors is essential for their function in the central nervous system.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; GABA&lt;sub&gt;A&lt;/sub&gt; receptors are assembled as pentamers from a specific combination of 19 subunits, including α1-α6 (GABRA1-A6), β1-β3 (GABRB1-B3), γ1-γ3 (GABRG1-G3), δ (GABRD), ϵ (GABRE), θ (GABRQ), π (GABRP), and ρ1-ρ3 (GABRR1-R3). The distribution of GABA&lt;sub&gt;A&lt;/sub&gt; receptors is throughout the brain regions, and the most abundant subtype is composed of two α1 subunits, two β2 subunits, and one γ2 subunit.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; To function, GABA&lt;sub&gt;A&lt;/sub&gt; receptor subunits need to fold in the endoplasmic reticulum (ER) with the assistance of molecular chaperones and subsequently assemble with other subunits to form heteropentamers. The properly assembled receptors exit the ER and traffic to the plasma membrane to act as chloride channels. Unassembled and misfolded subunits are retained in the ER, which could be routed to the degradation pathway by the ER-associated degradation.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; Recent quantitative proteomics analysis identified the proteostasis network that regulates the folding, assembly, trafficking, and degradation of GABA&lt;sub&gt;A&lt;/sub&gt; receptors.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;\u0000&lt;p&gt;Recent cryo-electron microscopy (cryo-EM) studies solved the high-resolution structures of pentameric GABA&lt;sub&gt;A&lt;/sub&gt; receptors, including α1β2γ2 receptors&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; and α1β3γ2 receptors.&lt;span&gt;&lt;sup&gt;12&lt;/sup&gt;&lt;/span&gt; The pentameric receptors are arranged as β-α1-β-α1-γ2 counterclockwise when viewed from the synaptic cleft (Figure 1A). Each pentamer has two binding sites for the neurotransmitter, GABA, at the interfaces between","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"33 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581952","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}

{"title":"Cystic Fibrosis Modulator Therapies: Bridging Insights from CF to other Membrane Protein Misfolding Diseases","authors":"Minsoo Kim, Lars Plate","doi":"10.1002/ijch.202300152","DOIUrl":"https://doi.org/10.1002/ijch.202300152","url":null,"abstract":"<h2> Conflict of interest</h2>\u0000<p>No conflicts to declare.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"1 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139553206","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}

{"title":"A RaPID Response to SARS-CoV-2","authors":"Sven Ullrich,&nbsp;Assoc. Prof. Christoph Nitsche","doi":"10.1002/ijch.202300170","DOIUrl":"10.1002/ijch.202300170","url":null,"abstract":"<p>Genetically encoded peptide libraries are at the forefront of <i>de novo</i> drug discovery. The RaPID (Random Nonstandard Peptides Integrated Discovery) platform stands out due to the unique combination of flexible <i>in vitro</i> translation (FIT) and mRNA display. This enables the incorporation of non-canonical amino acids, improving chemical diversity and allowing macrocyclisation of the peptide library. The resulting constrained peptides are valued for their strong binding affinity and stability, especially in the context of protein-protein interactions. In response to SARS-CoV-2, the causative agent of the COVID-19 pandemic, the RaPID system proved valuable in identifying high-affinity ligands of viral proteins. Among many peptide ligands of SARS-CoV-2 spike and main protease (M^pro), several macrocycles stand out for their exceptional binding affinities. Structural data showcases distinct binding modes in complex with the receptor-binding domain (RBD) of the spike glycoprotein or the catalytic active site of M^pro. However, translating these <i>in vitro</i> findings into clinical applications remains challenging, especially due to insufficient cell permeability.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 8-9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562231","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}