RSC Chemical Biology最新文献_第10页

Synthesis of 4-azido sialic acid for testing against Siglec-7 and in metabolic oligosaccharide engineering† 4-叠氮唾液酸的合成及其在低聚糖代谢工程中的应用。

IF 4.2

RSC Chemical Biology Pub Date : 2025-04-17 DOI: 10.1039/D5CB00030K

Taylor E. Gray, Kristin B. Labasan, Gour C. Daskhan, Duong T. Bui, Maju Joe, Dhanraj Kumawat, Edward N. Schmidt, John S. Klassen and Matthew S. Macauley

{"title":"Synthesis of 4-azido sialic acid for testing against Siglec-7 and in metabolic oligosaccharide engineering†","authors":"Taylor E. Gray, Kristin B. Labasan, Gour C. Daskhan, Duong T. Bui, Maju Joe, Dhanraj Kumawat, Edward N. Schmidt, John S. Klassen and Matthew S. Macauley","doi":"10.1039/D5CB00030K","DOIUrl":"10.1039/D5CB00030K","url":null,"abstract":"An important approach for tracking and visualizing sialic acid-containing glycans involves using sialic acid reporters functionalized with bioorthogonal handles. More specifically, metabolic oligosaccharide engineering (MOE) commonly employs monosaccharides with an alkyne or azide handle for incorporation into cellular glycans, followed by a subsequent click reaction to elaborate with a biotin or fluorophore handle. For sialic acid, this has been carried out extensively, with an azide or alkyne appended to the C5 N-acetamido group being the most common location for the handle. However, circumstances may require the handle to be at different positions and, to date, the C7 and C9 positions have been shown to work to varying degrees. Herein, we synthesized protected 4AzNeu5Ac that could be incorporated into cellular glycans nearly as efficiently as Neu5Az and targeted with DBCO-biotin through strain promoted azide–alkyne cycloaddition. Owing to the good incorporation of 4AzNeu5Ac into cellular glycans, we followed up this ability by first synthesizing the deprotected form of 4AzNeu5Ac, using a thioglycoside to lock the anomeric center during deprotection of the acetyl groups. Activation of 4AzNeu5Ac to CMP-4AzNeu5Ac then enabled the use of this donor by human sialyltransferase ST3GAL1 to transfer CMP-4AzNeu5Ac to β-Galp-(1→3)-α-GalpNAc. With purified α-4AzNeup5Ac-(2→3)-β-Galp-(1→3)-α-GalpNAc in hand, we tested it as a ligand for Siglec-7 and found that the C4-Az modification is tolerated, opening future possibilities to exploit this position to generate high affinity and selective ligands. These findings expand the repertoire of metabolic oligosaccharide engineering agents and show that azide modifications are tolerated at the C4 position of sialic acid.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 6","pages":" 869-881"},"PeriodicalIF":4.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057161","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

Structural and mechanistic insights into KslB, a bacterial Pictet–Spenglerase in kitasetaline biosynthesis† kitasetaline生物合成中细菌picet - spengl酶KslB的结构和机制研究。

IF 4.2

RSC Chemical Biology Pub Date : 2025-04-16 DOI: 10.1039/D5CB00070J

Wantae Kim, Ziyang Zheng, Kangsan Kim, Yu-Hsuan Lee, Hung-wen Liu and Y. Jessie Zhang

{"title":"Structural and mechanistic insights into KslB, a bacterial Pictet–Spenglerase in kitasetaline biosynthesis†","authors":"Wantae Kim, Ziyang Zheng, Kangsan Kim, Yu-Hsuan Lee, Hung-wen Liu and Y. Jessie Zhang","doi":"10.1039/D5CB00070J","DOIUrl":"10.1039/D5CB00070J","url":null,"abstract":"KslB is one of the few bacterial Pictet–Spenglerases recently identified in the biosynthesis of the β-carboline compound kitasetaline. While previous in vitro studies established that KslB catalyzes the condensation between L-tryptophan and α-ketoglutarate, the reaction mechanism, particularly its stereochemistry, remains poorly understood. This study presents five crystal structures of KslB, capturing key stages of reaction, shedding light on its catalytic dynamics. Among these, alternative binding poses of substrate and reaction product highlighted two significant features: (1) an additional pocket that accommodates L-tryptophan, and (2) two positively charged residues, Lys264 and Arg256, which form salt bridges with the product C1′ and C5′ carboxylate groups derived from α-ketoglutarate, ensuring a stereoselective process. These structural insights elucidate how KslB governs the stereochemistry of the cyclization process. Accordingly, we propose the configurations for the cyclized intermediate that align with the reaction's stereochemical outcome. Together, these findings offer valuable structural and mechanistic insights into KslB, paving the way for its potential engineering as a Pictet–Spengler biocatalyst.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 6","pages":" 933-941"},"PeriodicalIF":4.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003356","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

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