Israel Journal of Chemistry最新文献_第7页

Structure-Activity Relationships of 2-(Arylthio)benzoic Acid FTO Inhibitors 2-(芳硫基)苯甲酸 FTO 抑制剂的结构-活性关系

IF 3.2 4区化学

Israel Journal of Chemistry Pub Date : 2024-02-15 DOI: 10.1002/ijch.202300166

Chao Yan, Qian Zhang, Pan Xiao, Xinyun Xie, Ming Li, Yuanlai Qiu, Liufa Wen, Xiaomin Song, Ze Dong, Cai-Guang Yang

{"title":"Structure-Activity Relationships of 2-(Arylthio)benzoic Acid FTO Inhibitors","authors":"Chao Yan, Qian Zhang, Pan Xiao, Xinyun Xie, Ming Li, Yuanlai Qiu, Liufa Wen, Xiaomin Song, Ze Dong, Cai-Guang Yang","doi":"10.1002/ijch.202300166","DOIUrl":"10.1002/ijch.202300166","url":null,"abstract":"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 8c 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 in vitro. To enhance the antiproliferative effects in AML cell lines, we applied a prodrug strategy and prepared some esters. 7l, the methyl ester of 8l, exerted a superior inhibitory effect on a panel of AML cancer cell lines. Additionally, 7l 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.","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}

引用次数: 0

Recent Advance in the Study on 5-Formylcytosine (f5C) RNA Modification 5-甲酰基胞嘧啶 (f5C) RNA 修饰研究的最新进展

IF 3.2 4区化学

Israel Journal of Chemistry Pub Date : 2024-02-12 DOI: 10.1002/ijch.202300178

Xin Wang, Dr. Xiao-Yang Jin, Prof. Dr. Liang Cheng

引用次数: 0

Protein Glycosylation Patterns Shaped by the IRE1-XBP1s Arm of the Unfolded Protein Response 由折叠蛋白反应的 IRE1-XBP1s臂形成的蛋白质糖基化模式

IF 2.3 4区化学

Israel Journal of Chemistry Pub Date : 2024-02-05 DOI: 10.1002/ijch.202300162

Kenny Chen, Prof. Matthew D. Shoulders

{"title":"Protein Glycosylation Patterns Shaped by the IRE1-XBP1s Arm of the Unfolded Protein Response","authors":"Kenny Chen, Prof. Matthew D. Shoulders","doi":"10.1002/ijch.202300162","DOIUrl":"10.1002/ijch.202300162","url":null,"abstract":"The unfolded protein response (UPR) is a sensing and signaling pathway that surveys the endoplasmic reticulum (ER) for protein folding challenges and responds whenever issues are detected. UPR activation leads to upregulation of secretory pathway chaperones and quality control factors, as well as reduces the nascent protein load on the ER, thereby restoring and maintaining proteostasis. This paradigm-defining view of the role of the UPR is accurate, but it elides additional key functions of the UPR in cell biology. In particular, recent work has revealed that the UPR can shape the structure and function of N- and O-glycans installed on ER client proteins. This crosstalk between the UPR's reaction to protein misfolding and the regulation of glycosylation remains insufficiently understood. Still, emerging evidence makes it clear that the UPR, and particularly the IRE1-XBP1s arm of the UPR, may be a central regulator of protein glycosylation, with important biological consequences. In this review, we discuss the crosstalk between proteostasis, the UPR, and glycosylation, present progress towards understanding biological functions of this crosstalk, and examine potential roles in diseases such as cancer.","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300162","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ising Spins on Frustrated Bronze-Mean Hexagonal Quasicrystal 受挫铜平均六方准晶体的Ising自旋

IF 2.3 4区化学

Israel Journal of Chemistry Pub Date : 2024-01-30 DOI: 10.1002/ijch.202300113

Pratyay Ghosh

引用次数: 0

Nanopore Direct RNA Sequencing for Modified Uridine Nucleotides Yields Signals Dependent on the Physical Properties of the Modified Base 纳米孔对修饰的尿苷酸核苷酸进行直接 RNA 测序产生的信号取决于修饰碱基的物理特性

IF 3.2 4区化学

Israel Journal of Chemistry Pub Date : 2024-01-26 DOI: 10.1002/ijch.202300177

Prof. Aaron M. Fleming, Justin C. Dingman, Yizhou Wu, Spencer S. Hoon, Prof. Cynthia J. Burrows

{"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, Justin C. Dingman, Yizhou Wu, Spencer S. Hoon, Prof. Cynthia J. Burrows","doi":"10.1002/ijch.202300177","DOIUrl":"10.1002/ijch.202300177","url":null,"abstract":"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.","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}

引用次数: 0

Pathogenicity Prediction of GABAA Receptor Missense Variants GABAA 受体错义变异体的致病性预测

IF 2.3 4区化学

Israel Journal of Chemistry Pub Date : 2024-01-26 DOI: 10.1002/ijch.202300161

Ya-Juan Wang, Giang H. Vu, Ting-Wei Mu

{"title":"Pathogenicity Prediction of GABAA Receptor Missense Variants","authors":"Ya-Juan Wang, Giang H. Vu, Ting-Wei Mu","doi":"10.1002/ijch.202300161","DOIUrl":"10.1002/ijch.202300161","url":null,"abstract":"Variants in the genes encoding gamma-aminobutyric acid type A (GABAA) receptor subunits are associated with epilepsy. To date, over 1000 clinical variants have been identified in these genes. However, the majority of these variants lack functional studies and their clinical significance is uncertain although accumulating evidence indicates that proteostasis deficiency is the major disease-causing mechanism. Here, we apply two state-of-the-art modeling tools, namely AlphaMissense and Rhapsody to predict the pathogenicity of saturating missense variants in genes that encode the major subunits of GABAA receptors in the central nervous system, including GABRA1, GABRB2, GABRB3, and GABRG2. We demonstrate that the predicted pathogenicity correlates well between AlphaMissense and Rhapsody. In addition, AlphaMissense pathogenicity score correlates modestly with plasma membrane expression, peak current amplitude, and GABA potency of the variants that have available experimental data. Furthermore, almost all annotated pathogenic variants in the ClinVar database are successfully identified from the prediction, whereas uncertain variants from ClinVar partially due to the lack of experimental data are differentiated into different pathogenicity groups. The pathogenicity prediction of GABAA receptor missense variants provides a resource to the community as well as guidance for future experimental and clinical investigations.","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300161","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cystic Fibrosis Modulator Therapies: Bridging Insights from CF to other Membrane Protein Misfolding Diseases 囊性纤维化调节剂疗法：从囊性纤维化疾病到其他膜蛋白折叠错误疾病的知识桥梁

IF 2.3 4区化学

Israel Journal of Chemistry Pub Date : 2024-01-24 DOI: 10.1002/ijch.202300152

Minsoo Kim, Lars Plate

{"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":"10.1002/ijch.202300152","url":null,"abstract":"Cystic Fibrosis (CF) is a genetic disorder resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to a faulty CFTR protein. Dysfunctional CFTR causes chloride ion imbalance, resulting in dense mucus accumulation in various organs, particularly the lungs. CF treatments focus on symptom management and addressing CFTR′s functional defects. Notably, development of CFTR modulator therapies has significantly advanced CF treatment. These drugs target CFTR protein structural defects induced by mutations, restoring its function and improving CF symptoms. VX-770, a CFTR potentiator, and CFTR correctors like VX-809, VX-661, and VX-445, have gained FDA approval and widespread clinical use, greatly enhancing the health and survival of many CF patients. However, some CFTR mutations lack effective targeted therapies, leaving approximately 6 % of CF patients without suitable options. CFTR modulator therapies have proven essential for combating the underlying causes of protein misfolding diseases, serving as a blueprint for similar treatments in other membrane protein misfolding diseases. This review explores current and future CFTR modulator therapies, and applications of established paradigms to membrane protein misfolding diseases. Ongoing research and innovation hold the potential for further improvements in CF management and the treatment of protein misfolding diseases.","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 12","pages":""},"PeriodicalIF":2.3,"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}

引用次数: 0

A RaPID Response to SARS-CoV-2 RaPID 对 SARS-CoV-2 的回应

IF 2.3 4区化学

Israel Journal of Chemistry Pub Date : 2024-01-24 DOI: 10.1002/ijch.202300170

Sven Ullrich, Assoc. Prof. Christoph Nitsche

{"title":"A RaPID Response to SARS-CoV-2","authors":"Sven Ullrich, Assoc. Prof. Christoph Nitsche","doi":"10.1002/ijch.202300170","DOIUrl":"10.1002/ijch.202300170","url":null,"abstract":"Genetically encoded peptide libraries are at the forefront of de novo drug discovery. The RaPID (Random Nonstandard Peptides Integrated Discovery) platform stands out due to the unique combination of flexible in vitro 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 (Mpro), 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 Mpro. However, translating these in vitro findings into clinical applications remains challenging, especially due to insufficient cell permeability.","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}

引用次数: 0

30 Years of Semiconductor Nanowire Research: A Personal Journey 半导体纳米线研究 30 年：个人历程

IF 2.3 4区化学

Israel Journal of Chemistry Pub Date : 2024-01-19 DOI: 10.1002/ijch.202300127

Peidong Yang

引用次数: 0

Decoding Skd3 (Human CLPB): A Mitochondrial Protein Disaggregase Critical for Human Health 解码 Skd3（人类 CLPB）：对人类健康至关重要的线粒体蛋白分解酶

IF 2.3 4区化学

Israel Journal of Chemistry Pub Date : 2024-01-19 DOI: 10.1002/ijch.202300153

Ryan R. Cupo, Dr. James Shorter

引用次数: 0