RSC Chemical Biology最新文献_第9页

Contributors to the RSC Chemical Biology Emerging Investigators Collection 2024 贡献者的RSC化学生物学新兴研究人员收集2024。

IF 4.2

RSC Chemical Biology Pub Date : 2025-04-11 DOI: 10.1039/D5CB90017D

引用次数: 0

Contributors to the RSC Chemical Biology Emerging Investigators Collection 2024. 贡献者的RSC化学生物学新兴研究人员收集2024。

IF 4.2

RSC Chemical Biology Pub Date : 2025-04-11 eCollection Date: 2025-06-04 DOI: 10.1039/d5cb90017d

引用次数: 0

Epigenetic reader chromodomain as a potential therapeutic target 表观遗传解读器色域作为潜在的治疗靶点。

IF 4.2

RSC Chemical Biology Pub Date : 2025-04-11 DOI: 10.1039/D4CB00324A

Shivangi Sharma, J. Trae Hampton, Tatiana G. Kutateladze and Wenshe Ray Liu

{"title":"Epigenetic reader chromodomain as a potential therapeutic target","authors":"Shivangi Sharma, J. Trae Hampton, Tatiana G. Kutateladze and Wenshe Ray Liu","doi":"10.1039/D4CB00324A","DOIUrl":"10.1039/D4CB00324A","url":null,"abstract":"Epigenetic mechanisms involve cooperative actions of enzymes that produce or remove post-translational modifications in histones and ‘readers’, the protein domains that bind these modifications. Methylation of lysine residues represents one of the most common modifications and is recognized by a family of chromodomains. Chromodomain containing proteins are implicated in transcriptional regulation and chromatin remodeling, and aberrant functions of these proteins are linked to human diseases, such as cancer, neurodegenerative disorders and developmental abnormalities. In this work, we review biological and pathological activities of chromodomains, highlighting their potential as prognostic biomarkers and their attractiveness as therapeutic targets. In the past few years, significant progress has been made in the development of chromodomain inhibitors, however sequence similarity within this family of readers presents challenges in designing selective probes. We describe recent advances and new strategies that are employed to overcome these challenges, including structure-based drug design, high-throughput screening, the use of peptide and DNA encoded libraries, and summarize research underscoring the benefit of targeting chromodomains to combat diseases.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 6","pages":" 833-844"},"PeriodicalIF":4.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Photoaffinity enabled transcriptome-wide identification of splice modulating small molecule–RNA binding events in native cells† 光亲和使转录组范围内鉴定剪接调节小分子rna结合事件在天然细胞。

IF 4.2

RSC Chemical Biology Pub Date : 2025-04-03 DOI: 10.1039/D4CB00266K

Raven Shah, Wanlin Yan, Joyce Rigal, Steve Mullin, Lin Fan, Lynn McGregor, Andrew Krueger, Nicole Renaud, Andrea Byrnes and Jason R. Thomas

{"title":"Photoaffinity enabled transcriptome-wide identification of splice modulating small molecule–RNA binding events in native cells†","authors":"Raven Shah, Wanlin Yan, Joyce Rigal, Steve Mullin, Lin Fan, Lynn McGregor, Andrew Krueger, Nicole Renaud, Andrea Byrnes and Jason R. Thomas","doi":"10.1039/D4CB00266K","DOIUrl":"10.1039/D4CB00266K","url":null,"abstract":"Splice modulating small molecules have been developed to promote the U1 snRNP to engage with pre-mRNAs with strong and altered sequence preference. Transcriptomic profiling of bulk RNA from compound treated cells enables detection of RNAs impacted; however, it is difficult to delineate whether transcriptional changes are a consequence of direct compound treatment or trans-acting effects. To identify RNA targets that bind directly with splice modulating compounds, we deployed a photoaffinity labeling (PAL)-based Chem-CLIP approach. Through this workflow, we identify the telomerase lncRNA (TERC) as a previously unknown target of this class of clinically relevant small molecules. Using cellular ΔSHAPE-MaP, we orthogonally validate and further define the compound binding site as likely to be the conserved CR4/5 domain. Additionally, a thorough analysis of the PAL-based Chem-CLIP data reveals that considering competed RNAs, irrespective of magnitude of enrichment, adds a rich dimension of hit calling.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 6","pages":" 905-918"},"PeriodicalIF":4.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A stress-responsive p38 signaling axis in choanoflagellates† 鞭毛虫的应激反应p38信号轴。

IF 4.2

RSC Chemical Biology Pub Date : 2025-04-01 DOI: 10.1039/D4CB00122B

Florentine U. Rutaganira, Maxwell C. Coyle, Maria H. T. Nguyen, Iliana Hernandez, Alex P. Scopton, Arvin C. Dar and Nicole King

{"title":"A stress-responsive p38 signaling axis in choanoflagellates†","authors":"Florentine U. Rutaganira, Maxwell C. Coyle, Maria H. T. Nguyen, Iliana Hernandez, Alex P. Scopton, Arvin C. Dar and Nicole King","doi":"10.1039/D4CB00122B","DOIUrl":"10.1039/D4CB00122B","url":null,"abstract":"Animal kinases regulate cellular responses to environmental stimuli, including cell differentiation, migration, survival, and response to stress, but the ancestry of these functions is poorly understood. Choanoflagellates, the closest living relatives of animals, encode homologs of diverse animal kinases and have emerged as model organisms for reconstructing animal origins. However, efforts to identify key kinase regulators in choanoflagellates have been constrained by the limitations of currently available genetic tools. Here, we report on a framework that combines small molecule-driven kinase discovery with targeted genetics to reveal kinase function in choanoflagellates. To study the physiological roles of choanoflagellate kinases, we established two high-throughput platforms to screen the model choanoflagellate Salpingoeca rosetta with a curated library of human kinase inhibitors. We identified 95 diverse kinase inhibitors that disrupt S. rosetta cell proliferation. By focusing on one inhibitor, sorafenib, we identified a p38 kinase as a regulator of the heat shock response in S. rosetta. This finding reveals a conserved p38 function between choanoflagellates, animals, and fungi. Moreover, this study demonstrates that existing kinase inhibitors can serve as powerful tools to examine the ancestral roles of kinases that regulate modern animal development.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 6","pages":" 891-904"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell-penetrating peptide-conjugated, splice-switching oligonucleotides mitigate the phenotype in BTK/Tec double deficient X-linked agammaglobulinemia model† 细胞穿透肽偶联的剪接开关寡核苷酸减轻了BTK/Tec双缺陷x连锁无球蛋白血症模型的表型。

IF 4.2

RSC Chemical Biology Pub Date : 2025-03-31 DOI: 10.1039/D4CB00312H

Burcu Bestas, H. Yesid Estupiñán, Qing Wang, Shabnam Kharazi, Chenfei He, Dara K. Mohammad, Dhanu Gupta, Oscar P. B. Wiklander, Taavi Lehto, Karin E. Lundin, Anna Berglöf, Mikael C. I. Karlsson, Frank Abendroth, Samir El Andaloussi, Michael J. Gait, Matthew J. A. Wood, Christian J. Leumann, Dmitry A. Stetsenko, Robert Månsson, Jesper Wengel, Rula Zain and C. I. Edvard Smith

{"title":"Cell-penetrating peptide-conjugated, splice-switching oligonucleotides mitigate the phenotype in BTK/Tec double deficient X-linked agammaglobulinemia model†","authors":"Burcu Bestas, H. Yesid Estupiñán, Qing Wang, Shabnam Kharazi, Chenfei He, Dara K. Mohammad, Dhanu Gupta, Oscar P. B. Wiklander, Taavi Lehto, Karin E. Lundin, Anna Berglöf, Mikael C. I. Karlsson, Frank Abendroth, Samir El Andaloussi, Michael J. Gait, Matthew J. A. Wood, Christian J. Leumann, Dmitry A. Stetsenko, Robert Månsson, Jesper Wengel, Rula Zain and C. I. Edvard Smith","doi":"10.1039/D4CB00312H","DOIUrl":"10.1039/D4CB00312H","url":null,"abstract":"Splice-switching oligonucleotides (SSOs) have been developed as a treatment for various disorders, including Duchenne muscular dystrophy and spinal muscular atrophy. Here, the activity of several different SSOs was investigated as potential treatments for B lymphocyte disorders with a focus on X-linked agammaglobulinemia (XLA), caused by defects in the gene encoding Bruton's tyrosine kinase (BTK). In this study, the activity of locked nucleic acid (LNA), tricyclo-DNA (tcDNA), phosphoryl guanidine oligonucleotides (PGO) and phosphorodiamidate morpholino oligomers (PMO) were compared, targeting the pseudoexon region of BTK pre-mRNA. We further investigated the effect of conjugating cell-penetrating peptides, including Pip6a, to the SSOs. The effect was measured as splice-switching in vitro as well as in a further developed, bacterial artificial chromosome transgenic mouse model of XLA. Therapy in the form of intravenous infusions 2 times a week during 3 weeks of PMO oligomers conjugated to Pip6a was sufficient to partly restore the in vivo B lineage phenotype. SSOs treatment also provides a unique opportunity to get insights into a restoration process, when B lymphocytes of different maturation stages are simultaneously splice-corrected.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 5","pages":" 761-771"},"PeriodicalIF":4.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enzyme-mediated proximity labeling reveals the co-translational targeting of DLGAP5 mRNA to the centrosome during mitosis† 酶介导的接近标记揭示了DLGAP5 mRNA在有丝分裂过程中对中心体的共翻译靶向。

IF 4.2

RSC Chemical Biology Pub Date : 2025-03-26 DOI: 10.1039/D4CB00155A

Gang Wang, Mo Li and Peng Zou

引用次数: 0

3′-O-β-Glucosylation of nucleoside analogues using a promiscuous bacterial glycosyltransferase† 使用混杂细菌糖基转移酶的核苷类似物的3'-O-β-糖基化。

IF 4.2

RSC Chemical Biology Pub Date : 2025-03-25 DOI: 10.1039/D5CB00026B

Jonathan P. Dolan, Tessa Keenan, Aisling Ní Cheallaigh, Martin A. Fascione and Gavin J. Miller

引用次数: 0

Synthetic biology routes to new and extinct natural products 合成生物学途径新的和已灭绝的天然产品。

IF 4.2

RSC Chemical Biology Pub Date : 2025-03-21 DOI: 10.1039/D5CB00047E

Thomas J. Simpson

{"title":"Synthetic biology routes to new and extinct natural products","authors":"Thomas J. Simpson","doi":"10.1039/D5CB00047E","DOIUrl":"10.1039/D5CB00047E","url":null,"abstract":"Recent developments in genome sequencing and genetic engineering have revolutionised elucidation of biosynthetic pathways in bacteria and fungi and allowed production of new natural products and engineered strains with optimised production of new and/or preferred metabolites. The clinically important antibiotic mupirocin is a mixture of closely related pseudomonic acids produced by Pseudomonas fluorescens via a trans-AT modular PKS. Extensive gene knock-out experiments have led to the isolation of a plethora of new metabolites: both biosynthetic intermediates and shunt products. Parallel experiments, along with swapping of biosynthetic genes, with a Pseudoalteromonas sp. which produces the closely related thiomarinols give similar results and many new products. A genetically engineered strain of P. fluorescens produces high titres of a single pseudomonic acid with improved stability and antibiotic properties. Tenellin and bassianin are insecticidal fungal metabolites produced by Beauvaria species via multi-domain PKS-NRPSs. Heterologous expression in Aspergillus oryzae of hybrid systems produced by domain swapping between the two biosynthetic gene clusters produce many new metabolites in high yields and reveal the key elements in control of polyketide chain length and methylation, showing the potential for combinatorial biosynthesis of these and related metabolites. Cryptosporiopsis sp. 8999 produces three related dimeric xanthones. Gene knock-outs allow elucidation of the full biosynthetic pathway, isolation of the monomeric precursor and engineering of a strain producing only the major component of the wild-type mixture.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 5","pages":" 721-730"},"PeriodicalIF":4.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thiophosphate bioisosteres of inositol hexakisphosphate enhance binding affinity and residence time on bacterial virulence factors† 六磷酸肌醇的硫代磷酸生物异构体增强了对细菌毒力因子的结合亲和力和停留时间。

IF 4.2

RSC Chemical Biology Pub Date : 2025-03-20 DOI: 10.1039/D4CB00228H

Rebecca Cummer, Garvit Bhatt, Lauren M. Finn, Bettina G. Keller, Bhushan Nagar and Bastien Castagner

{"title":"Thiophosphate bioisosteres of inositol hexakisphosphate enhance binding affinity and residence time on bacterial virulence factors†","authors":"Rebecca Cummer, Garvit Bhatt, Lauren M. Finn, Bettina G. Keller, Bhushan Nagar and Bastien Castagner","doi":"10.1039/D4CB00228H","DOIUrl":"10.1039/D4CB00228H","url":null,"abstract":"Inositol phosphates are essential for mammalian cell signalling with critical roles in cellular processes. The fully phosphorylated inositol phosphate, myo-inositol hexakisphosphate (IP6), modulates numerous eukaryotic proteins and bacterial virulence factors. It has been suggested that the high charge density of IP6 causes restructuring of virulence factors in mammalian cells, activating their enzymatic activity. IP6 is challenging to study due to its phytase instability and propensity to precipitate. Here we suggest that the thiophosphate bioisostere, myo-inositol hexakisthiophosphate (IT6), will mitigate these issues, as thiophosphate substitution has been found to be phytase resistant and improve solubility. Assessment of the chemical properties of IT6 has indeed validated these characteristics. In addition, we performed biophysical characterization of IT6 binding to the virulence factors Salmonella enterica serovar Typhimurium AvrA, Vibrio parahaemolyticus VopA, and Clostridioides difficile TcdB. Our data show that the higher charge density of IT6 increased its binding affinity and residence time on the proteins, which improved stabilization of the bound-state. IT6 is a valuable tool for structural biology research and the described biophysical characteristics of thiophosphate substitution are of value in medicinal chemistry.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 6","pages":" 882-890"},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0