Israel Journal of Chemistry最新文献

{"title":"Pharmacologic Targeting of PDIA1 Inhibits NLRP3 Inflammasome Assembly and Activation","authors":"Jessica D. Rosarda,&nbsp;Caroline R. Stanton,&nbsp;Emily B. Chen,&nbsp;Michael J. Bollong,&nbsp;R. Luke Wiseman","doi":"10.1002/ijch.202300125","DOIUrl":"10.1002/ijch.202300125","url":null,"abstract":"<p>The NLRP3 inflammasome is a cytosolic protein complex that regulates innate immune signaling in response to diverse pathogenic insults through the proteolytic processing and secretion of pro-inflammatory cytokines such as IL-1β. Hyperactivation of NLRP3 inflammasome signaling is implicated in the onset and pathogenesis of numerous diseases, motivating the discovery of new strategies to suppress NLRP3 inflammasome activity. We sought to define the potential for the proteostasis regulator AA147 to inhibit the assembly and activation of the NLRP3 inflammasome. AA147 is a pro-drug that is metabolically converted to a reactive metabolite at the endoplasmic reticulum (ER) membrane to covalently modify ER-localized proteins such as protein disulfide isomerases (PDIs). We show that AA147 inhibits NLRP3 inflammasome activity in monocytes and monocyte-derived macrophages through a mechanism involving impaired assembly of the active inflammasome complex. This inhibition is mediated through AA147-dependent covalent modification of PDIA1. Genetic depletion or treatment with other highly selective PDIA1 inhibitors similarly blocks NLRP3 inflammasome assembly and activation. Our results identify PDIA1 as a potential therapeutic target to mitigate NLRP3 inflammasome-mediated pro-inflammatory signaling implicated in etiologically diverse diseases.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135341332","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":"The Role of the Proteasome in Limiting Cellular Stress Associated with Protein Accumulation","authors":"Kate A. Kragness,&nbsp;Darci J. Trader","doi":"10.1002/ijch.202300120","DOIUrl":"10.1002/ijch.202300120","url":null,"abstract":"<p>The proteasome is comprised of multiple subunits that catalyze the degradation of proteins to maintain cellular homeostasis. The proteasome targets protein substrates by two different pathways. The ubiquitin-dependent pathway requires proteins to be labeled with a ubiquitin tag to signal for degradation by the 26S isoform of the proteasome. Protein degradation through this pathway declines during age progression. The ubiquitin-independent pathway utilizes the 20S proteasome isoform. It can degrade misfolded and intrinsically disordered proteins to decrease cellular stress. Age-related protein accumulation and aggregation can occur due to the decreased activity and expression of the proteasome. Protein accumulation causes increased cellular stress which can contribute to disease progression. Increasing proteasome activity could serve as a solution to eliminating and preventing protein accumulation. Studies have shown the value of the proteasome as a therapeutic entity to mitigate cellular stress. This perspective explores the link between proteasome activity and cellular stress caused by age-related misfolded protein accumulation.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135480424","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":"Understanding and Overcoming Biochemical Diversity in AL Amyloidosis","authors":"Gareth J. Morgan","doi":"10.1002/ijch.202300128","DOIUrl":"10.1002/ijch.202300128","url":null,"abstract":"<p>Amyloid fibril deposition causes progressive tissue damage and organ failure in the systemic amyloid diseases, and therapies that suppress aggregation lead to clinical benefit. Small molecules that prevent aggregation by binding to precursor proteins are effective for amyloid transthyretin (ATTR) amyloidosis. However, in amyloid light chain (AL) amyloidosis, fibrils are formed by antibody light chains and every patient has a unique protein sequence that aggregates. The highly diverse sequences of these light chains appear to determine whether an individual is at risk of amyloidosis, the distribution of amyloid deposits and the progression of disease. Light chains are therefore challenging drug targets. This review explores the parallels between AL amyloidosis and ATTR amyloidosis to describe the discovery of small molecules that can stabilize light chains. These molecules have potential as therapies for AL amyloidosis, highlighting potential opportunities for drug discovery in other diseases of protein misfolding.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135679326","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":"Scanning Tunnelling Microscopy Studies of Tsai-Type Quasicrystal Approximants","authors":"Dr. Sam Coates,&nbsp;Dominic Burnie,&nbsp;Dr. Hem Raj Sharma,&nbsp;Ronan McGrath","doi":"10.1002/ijch.202300116","DOIUrl":"10.1002/ijch.202300116","url":null,"abstract":"<p>We review scanning tunnelling microscopy (STM) studies of the surfaces of periodic Tsai-type approximants. Although they are useful analogues to the Tsai-type quasicrystals, the surfaces of these periodic approximants behave in subtly different and often more complex ways when compared to their quasiperiodic cousins. We present a summary of STM studies conducted upon Tsai-type approximants; we discuss the various differences and similarities between phases and surface directions, and compare these to the surfaces of the related quasicrystalline phases. We also present open questions which have been raised by these studies, and offer potential routes to answer them.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135973475","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":"Quasicrystal Structure Prediction: A Review","authors":"Michael Widom,&nbsp;Marek Mihalkovič","doi":"10.1002/ijch.202300122","DOIUrl":"10.1002/ijch.202300122","url":null,"abstract":"<p>Predicting quasicrystal structures is a multifaceted problem that can involve predicting a previously unknown phase, predicting the structure of an experimentally observed phase, or predicting the thermodynamic stability of a given structure. We survey the history and current state of these prediction efforts with a focus on methods that have improved our understanding of the structure and stability of known metallic quasicrystal phases. Advances in the structural modeling of quasicrystals, along with first principles total energy calculation and statistical mechanical methods that enable the calculation of quasicrystal thermodynamic stability, are illustrated by means of cited examples of recent work.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136079036","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":"A Quantitative Sequencing Method for 5-Formylcytosine in RNA","authors":"Ruitu Lyu,&nbsp;Kinga Pajdzik,&nbsp;Hui-Lung Sun,&nbsp;Linda Zhang,&nbsp;Li-Sheng Zhang,&nbsp;Tong Wu,&nbsp;Lei Yang,&nbsp;Tao Pan,&nbsp;Chuan He,&nbsp;Qing Dai","doi":"10.1002/ijch.202300111","DOIUrl":"10.1002/ijch.202300111","url":null,"abstract":"<p>5-Formylcytosine (f⁵C) modification is present in human mitochondrial methionine tRNA (mt-tRNA^Met) and cytosolic leucine tRNA (ct-tRNA^Leu), with their formation mediated by NSUN3 and ALKBH1. f⁵C has also been detected in yeast mRNA and human tRNA, but its transcriptome-wide distribution in mammals has not been studied. Here we report f⁵C-seq, a quantitative sequencing method to map f⁵C transcriptome-wide in HeLa and mouse embryonic stem cells (mESCs). We show that f⁵C in RNA can be reduced to dihydrouracil (DHU) by pic-borane, and DHU can be exclusively read as T during reverse transcription (RT) reaction, allowing the detection and quantification of f⁵C sites by a unique C-to-T mutation signature. We validated f⁵C-seq by identifying and quantifying the two known f⁵C sites in tRNA, in which the f⁵C modification fractions dropped significantly in ALKBH1-depleted cells. By applying f⁵C-seq to chromatin-associated RNA (caRNA), we identified several highly modified f⁵C sites in HeLa and mouse embryonic stem cells (mESC).</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 3-4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136079035","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":"The Cellular Environment Guides Self-Assembly and Structural Conformations of Microtubule-Associated Protein Tau (MAPT)","authors":"Kelly M. Montgomery,&nbsp;Avi J. Samelson,&nbsp;Jason E. Gestwicki","doi":"10.1002/ijch.202300104","DOIUrl":"10.1002/ijch.202300104","url":null,"abstract":"<p>In neurodegenerative tauopathies, such as Alzheimer's disease (AD), microtubule-associated protein tau (MAPT/tau) transitions from a soluble form to insoluble, filamentous lesions inside affected neurons. During this process, tau adopts a range of physical configurations: from misfolded monomers to higher-order oligomers and fibrils. Tau aggregation is also associated with changes in post-translational modifications (PTMs), such as ubiquitination, oxidation, glycation, hyper-phosphorylation and acetylation, which collectively produce an impressive range of possible tau proteoforms. Many of these tau proteoforms are highly cationic and unlikely to self-assemble without neutralization of their charges. Indeed, tau fibrils from patients contain anionic biomacromolecules and bound proteins, suggesting that cytosolic components contribute to fibrilligenesis. Here, we review what is known about how the cytosol impacts tau's aggregation pathways. We also speculate that the composition of each brain region (<i>e. g</i>., redox state, tau proteoforms, levels of permissive polyanions, <i>etc</i>.) might play an active role in shaping the structure of the resulting tau fibrils. Although much remains to be discovered, a greater understanding of the role of the cytosol on tau self-assembly might lead to identification of new therapeutic targets.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135146185","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":"Surface Reactivity of the Au-Si-Ho Quasicrystalline 1/1 Approximant","authors":"Wilfried Bajoun Mbajoun,&nbsp;Yu-Chin Huang,&nbsp;Girma Hailu Gebresenbut,&nbsp;Cesar Pay Gómez,&nbsp;Vincent Fournée,&nbsp;Julian Ledieu","doi":"10.1002/ijch.202300118","DOIUrl":"10.1002/ijch.202300118","url":null,"abstract":"<p>The oxidation of the (100) surface of Au-Si-Ho quasicrystalline approximant was studied using low-energy electron diffraction and X-ray photoelectron spectroscopy. The combination of these two techniques provides evidence for a Ho and Si surface segregation induced by O₂ adsorption, resulting in the loss of surface long-range order.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 10-11","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135590457","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":"Π-acid catalysis – challenges, advances, and opportunities","authors":"Dr. Yuri Tulchinsky,&nbsp;Prof. Ehud Keinan","doi":"10.1002/ijch.202300132","DOIUrl":"https://doi.org/10.1002/ijch.202300132","url":null,"abstract":"&lt;p&gt;Π-acid catalysis is one of the last two decades′ most exciting developments in synthetic organic chemistry. Because of the mild conditions employed and high functional group tolerance, π-acid catalysis became a tool of choice for the selective activation of double and triple C−C bonds at the late stages of multistep syntheses. At the same time, owing to the simplicity of the reaction setup, it also provides an easy and atom-economic route towards a broad array of valuable precursors.&lt;/p&gt;&lt;p&gt;Traditionally, the field of π-acid catalysis has relied on complexes of Au(I) and Pt(II). These electron-rich cations are well-suited for the carbophilic activation of C−C multiple bonds. On the one hand, they are highly polarizable and hence can efficiently interact with the &lt;i&gt;η&lt;/i&gt;&lt;sub&gt;2&lt;/sub&gt;-coordinated “soft” alkene or alkyne ligands. Yet, on the other hand, they are sufficiently electrophilic to render those ligands susceptible to nucleophilic attacks. While gold and platinum still maintain their privileged position in π-acid catalysis, the growing list of metals employable as π-acid catalysts now includes not only other noble elements (Pd, Rh, etc.), but also some earth-abundant ones, such as Cu, Zn, and even Al, providing cheaper alternatives for the precious metals.&lt;/p&gt;&lt;p&gt;The choice of ancillary ligands plays a crucial role in imparting an electrophilic character on metal centers for use as π-acid catalysts. New strong electron-withdrawing ancillary ligands were developed in search of better catalysts. A possible way to achieve this goal is by increasing the π-acidity of moderately π-acidic ligands, such as tertiary phosphines and N-heterocyclic carbenes (NHCs). In the present issue, two contributions - a communication by Manuel Alcarazo and a research article by Fumitoshi Shibahara - represent this endeavor.&lt;/p&gt;&lt;p&gt;Prof. Alcarazo is renowned for introducing the α-cationic phosphines and arsines as a novel class of highly π-acidic ancillary ligands for catalysis, mostly in Au(I) and Pt(II) systems. In recent years, his group has been active in developing asymmetric π-acid catalysis with chiral α-cationic phosphinates. A short communication presented in this issue describes the application of these unusual ancillary ligands for a highly enantioselective one-pot preparation of chiral &lt;i&gt;C&lt;sub&gt;2&lt;/sub&gt;&lt;/i&gt;-symmetric [5]helicenes with two peripheral axial stereogenic centers. Asymmetric π-acid catalysis by Au(I) and Au(III) complexes is thoroughly addressed in a comprehensive review by Nitin Patil. Surprisingly, despite the prominent role of Au in π-acid catalysis in general, chiral gold catalysts have received much less attention. Prof. Patil's review aims at filling in this lacune and provides a retrospect of the significant developments in this area during the last 15 years.&lt;/p&gt;&lt;p&gt;A research article by Prof. Shibahara presents a different kind of π-acidic ancillary ligands. His group reports on a novel series of fused NHC ligands with electron-withdra","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"63 9","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50130822","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":"Recent Applications of Paired Electrolysis in Organic Synthesis","authors":"Ke-Jin Jiao,&nbsp;Xiao-Tong Gao,&nbsp;Cong Ma,&nbsp;Ping Fang,&nbsp;Tian-Sheng Mei","doi":"10.1002/ijch.202300085","DOIUrl":"10.1002/ijch.202300085","url":null,"abstract":"<p>Recent years have witnessed a renaissance of organic electrochemistry since the cheap, safe, sustainable electron could be employed as a traceless redox agent to facilitate redox conversions. Additionally, divergent selectivity could be achieved by tuning the potential or current of the electrochemical reaction. Compared to electrooxidation or electroreduction reactions, paired electrolysis represents a more practical and energy-efficient strategy that delivers the products by making use of both anodic and cathodic reactions simultaneously. This mini-review summarized the breakthroughs and recent advances in this fascinating field and mainly is divided into three parts: parallel, sequential, and convergent paired electrolysis.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 1-2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135536604","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}