RSC Chemical Biology最新文献

P450 cyptide synthase MpoB catalyzes the cross-linking of the YPW motif on the precursor peptide. P450 cyptide synthase MpoB催化前体肽上YPW基序的交联。

IF 3.1

RSC Chemical Biology Pub Date : 2025-07-24 DOI: 10.1039/d5cb00153f

Abujunaid Habib Khan, Jabal Rahmat Haedar, Vic Kiselov, Viktors Romanuks, Gints Smits, Stefano Donadio, Chin-Soon Phan

引用次数: 0

Semi-enzymatic synthesis and application of ¹³C-isotopically labelled inositol-(1,4,5)-trisphosphate. 13c -同位素标记肌醇-(1,4,5)-三磷酸的半酶合成及应用。

IF 3.1

RSC Chemical Biology Pub Date : 2025-07-23 DOI: 10.1039/d5cb00139k

Atharva Patharkar, Meike Amma, Jaime Isern, Zoé Chaudron, Angélique Besson-Bard, Valérie Nicolas-Francès, Claire Rosnoblet, David Wendehenne, Peter Schmieder, Dorothea Fiedler

{"title":"Semi-enzymatic synthesis and application of 13C-isotopically labelled inositol-(1,4,5)-trisphosphate.","authors":"Atharva Patharkar, Meike Amma, Jaime Isern, Zoé Chaudron, Angélique Besson-Bard, Valérie Nicolas-Francès, Claire Rosnoblet, David Wendehenne, Peter Schmieder, Dorothea Fiedler","doi":"10.1039/d5cb00139k","DOIUrl":"10.1039/d5cb00139k","url":null,"abstract":"Inositol-(1,4,5)-trisphosphate (Ins(1,4,5)P3) is a crucial secondary messenger that controls calcium (Ca2+) levels inside cells, yet many questions regarding Ins(1,4,5)P3 metabolism are challenging to address with current methods. Here, a semi-enzymatic milligram scale synthesis of isotopically labeled [13C6]Ins(1,4,5)P3 is reported which then served as a substrate to monitor the activity of mammalian type II inositol 1,4,5-trisphosphate 5-phosphatase INPP5B, using NMR spectroscopy in real time. In addition, the phosphorylation sequence catalyzed by inositol polyphosphate multikinase IPMK was confirmed using [13C6]Ins(1,4,5)P3 and 2D NMR spectroscopy. The method was subsequently applied to characterize the phosphorylation/dephosphorylation reactions of a putative inositol phosphate kinase from the alga Klebsormidium nitens (KnIPK2). KnIPK2 displayed 6-kinase activity towards [13C6]Ins(1,4,5)P3, and dual 4/6- and 5-phosphatase activity towards [13C6]Ins(1,3,4,5,6)P5. Finally, [13C6]Ins(1,4,5)P3 was utilized as an internal standard in hydrophilic liquid interaction chromatography mass spectrometry (HILIC-MS) experiments, to quantify dephosphorylation of Ins(1,4,5)P3 by INPP5B. [13C6]Ins(1,4,5)P3 therefore constitutes a broadly applicable analytical tool that should facilitate the characterization of Ins(1,4,5)P3 metabolism in the future.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745397","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

Defining STING-sterol interactions with chemoproteomics. 用化学蛋白质组学定义sting -甾醇相互作用。

IF 3.1

RSC Chemical Biology Pub Date : 2025-07-21 DOI: 10.1039/d5cb00171d

Ian Ford, Miranda Villanueva, Min Sub Lee, Quan D Zhou, Constance Yuen, Robert Damoiseaux, Steven J Bensinger, Keriann M Backus

{"title":"Defining STING-sterol interactions with chemoproteomics.","authors":"Ian Ford, Miranda Villanueva, Min Sub Lee, Quan D Zhou, Constance Yuen, Robert Damoiseaux, Steven J Bensinger, Keriann M Backus","doi":"10.1039/d5cb00171d","DOIUrl":"https://doi.org/10.1039/d5cb00171d","url":null,"abstract":"Stimulator of interferon genes (STING) is an intracellular pattern recognition receptor that plays a key role in responding to cytosolic DNA and cyclic dinucleotides. STING activity is tightly regulated to avoid aberrant STING activity, excessive type I IFN responses, and resultant autoinflammatory disease. As such understanding the molecular events regulating STING activity is critical. Recent work has revealed cellular cholesterol metabolism also functions to modulate STING activity, although the molecular events linking cholesterol homeostasis with STING remain incompletely understood. Here we pair genetic and chemoproteomic approaches to inform the mechanisms governing cholesterol modulation of STING activity. Using gain- and loss-of-function systems, we find that markedly increasing SCAP-SREBP2 processing and resultant cholesterol synthesis has little impact on STING activity. In contrast, we find that genetic deletion of Srebf2 increased basal and ligand inducible type I IFN responses. Thus, STING can function in the absence of the SCAP-SREBP2 protein apparatus. Through activity-based protein profiling with three distinct sterol-mimetic probes, we provide direct evidence for STING-sterol binding. We also find that the mitochondrial protein VDAC1 co-purifies with STING and binds to sterol-mimetic probes. We also show that STING's subcellular localization is responsive to modulation of cellular sterol content. Our findings support a model where sterol synthesis in the ER regulates STING activity, aligning with recent studies indicating that cholesterol-mediated retention of STING in the endoplasmic reticulum occurs through cholesterol recognition amino acid consensus (CARC) motifs in STING.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761718","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

Synergy of triazolyl substituents at C1 and C3 of galactose for high-affinity and selective galectin-4C inhibition. 半乳糖C1和C3上的三唑基取代基协同作用对半乳糖凝集素- 4c的高亲和力和选择性抑制。

IF 3.1

RSC Chemical Biology Pub Date : 2025-07-18 DOI: 10.1039/d5cb00106d

Alexander Dahlqvist, Rob Marc Go, Chandan Kishor, Hakon Leffler, Helen Blanchard, Ulf J Nilsson

{"title":"Synergy of triazolyl substituents at C1 and C3 of galactose for high-affinity and selective galectin-4C inhibition.","authors":"Alexander Dahlqvist, Rob Marc Go, Chandan Kishor, Hakon Leffler, Helen Blanchard, Ulf J Nilsson","doi":"10.1039/d5cb00106d","DOIUrl":"10.1039/d5cb00106d","url":null,"abstract":"Galectins are a family of carbohydrate-recognising proteins involved in regulation of cell adhesion and cell signaling, leading to roles in e.g. cancer progression, fibrosis, and ulcerative colitis. Glycomimetic galectin inhibitors based on different molecular scaffolds are known and have demonstrated effects from cell experiments to the clinic. Presented here is the synthesis and evaluation of 3-aryltriazolyl-C1-galactosyls leading to discovery of an unexpected synergy effect between C1 and C3 triazolyl substituents to give galectin-4C (C-terminal domain) inhibitors with affinities down to 9.5 μM and up to thirty-sevenfold selectivity for galectin-4C over other galectins. X-ray structural analysis of one inhibitor:galectin-4C complex revealed that both the C1 and C3 arene-substituents engage in interactions with the galectin-4C binding site. These molecules have potential as lead compounds towards discovery of galectin-4-targeting compounds addressing inflammatory conditions, such as inflammatory bowel disease and ulcerative colitis.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745398","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

Regioselective rapid ene-type reaction (RRER) enables bioconjugation of histone serotonylation† 区域选择性快速基因型反应（RRER）使组蛋白5 -羟色胺化的生物偶联。

IF 3.1

RSC Chemical Biology Pub Date : 2025-07-17 DOI: 10.1039/D5CB00159E

Jinghua Wu, Huapeng Li, Adam R. Lovato, Andrew Symasek, Zeng Lin and Qingfei Zheng

{"title":"Regioselective rapid ene-type reaction (RRER) enables bioconjugation of histone serotonylation†","authors":"Jinghua Wu, Huapeng Li, Adam R. Lovato, Andrew Symasek, Zeng Lin and Qingfei Zheng","doi":"10.1039/D5CB00159E","DOIUrl":"10.1039/D5CB00159E","url":null,"abstract":"Triazolinedione (TAD) derivatives have been commonly utilized as protection and labeling reagents for indole and phenol moieties via a reversible ene-type reaction. Previous studies showed that the TAD probes could selectively modify tyrosine and tryptophan side-chains within proteins and peptides under distinct pH conditions. Here, we report a pH-controlled regioselective rapid ene-type reaction (RRER) between TAD and 5-hydroxyindole, where the modification occurs on the C4 position rather than the C3 of inactivated indole rings. Employing this unique reaction, we have performed the selective bioconjugation of serotonylation occurring on the fifth amino acid residue, glutamine, of histone H3 (H3Q5), which does not contain any tryptophan in its protein sequence. Finally, RRER was applied to determine the H3Q5 serotonylation levels in cultured cells and tissue samples, which served as a newly developed powerful tool for in vitro and in vivo histone monoaminylation analysis. Overall, our findings in this research expanded the chemical biology toolbox for investigating histone monoaminylation and facilitated the understandings of TAD-mediated ene-type reactions.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1278-1283"},"PeriodicalIF":3.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699844","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

Chemoenzymatic synthesis of sialylated and fucosylated mucin analogs reveals glycan-dependent effects on protein conformation and degradation† 唾液化和聚焦化黏蛋白类似物的化学酶合成揭示了聚糖对蛋白质构象和降解的依赖作用。

IF 3.1

RSC Chemical Biology Pub Date : 2025-07-14 DOI: 10.1039/D5CB00111K

Amanda M. Wood, Casia L. Wardzala and Jessica R. Kramer

{"title":"Chemoenzymatic synthesis of sialylated and fucosylated mucin analogs reveals glycan-dependent effects on protein conformation and degradation†","authors":"Amanda M. Wood, Casia L. Wardzala and Jessica R. Kramer","doi":"10.1039/D5CB00111K","DOIUrl":"10.1039/D5CB00111K","url":null,"abstract":"Mucin proteins are essential for life but are challenging to study due to their complex glycosylation patterns. Synthetic mimics have become vital tools for understanding and modulating the roles of mucins in human health and disease. These materials also have diverse biomedical applications as lubricants and anti-infectives, in vaccine formulations, and more. We developed a chemoenzymatic approach to prepare polypeptide-based synthetic mucins displaying a variety of glycans with native linkages and orientations. By combining the polymerization of glycosylated amino acid N-carboxyanhydrides with enzymatic sialylation and fucosylation, we produced a tunable panel of synthetic mucins. These polymers were recognized by natural glycan-binding and glycan-degrading enzymes, providing insights into the structural preferences of these proteins. Glycan- and linkage-dependent effects on proteolysis were observed. Further, investigation of the influence of glycans on peptide backbone secondary structure revealed that both sialylation and linkage at Ser vs. Thr have profound effects on hierarchical conformation. Overall, our methodology offers versatile tools for exploring the diverse glycobiology of mucins.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1336-1352"},"PeriodicalIF":3.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660696","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

Random peptide mixtures of tryptophan and lysine suppress the aggregation of a cancer-related mutant of the Axin protein† 色氨酸和赖氨酸的随机肽混合物抑制了与癌症相关的轴蛋白突变体的聚集。

IF 3.1

RSC Chemical Biology Pub Date : 2025-07-10 DOI: 10.1039/D5CB00141B

Tommaso Garfagnini, Zvi Hayouka and Assaf Friedler

{"title":"Random peptide mixtures of tryptophan and lysine suppress the aggregation of a cancer-related mutant of the Axin protein†","authors":"Tommaso Garfagnini, Zvi Hayouka and Assaf Friedler","doi":"10.1039/D5CB00141B","DOIUrl":"10.1039/D5CB00141B","url":null,"abstract":"Aggregation of dysfunctional proteins can lead to a variety of diseases including cancer. We have previously developed chaperone-derived peptides that inhibit aggregation of the cancer-related L106R mutant of Axin RGS. Here we show that significantly improved inhibition was achieved using random peptide mixtures (RPMs) designed to mimic the chemical characteristics of the chaperone-like peptides. 20-mer RPMs of tryptophan and lysine suppressed aggregation of Axin RGS L106R with up to 50-fold improved activity compared to parent inhibitors. Conversely, peptides derived from the lead hotspot of Axin RGS aggregation that were designed to be specific, were unable to prevent aggregation of the protein. RPMs constitute the most efficient strategy to date to magnify peptide inhibitory activity against Axin RGS L106R aggregation, as they contain multiple active species and conformations that cover a larger inhibitory space and shield multiple hotspots at once. Our results demonstrate that the chemical composition of the peptide, and not the specific sequence, is the key factor for inhibitory activity.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1270-1277"},"PeriodicalIF":3.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12264706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660697","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

Outstanding Reviewers for RSC Chemical Biology in 2024 2024年RSC化学生物学杰出审稿人

IF 3.1

RSC Chemical Biology Pub Date : 2025-07-08 DOI: 10.1039/D5CB90026C

引用次数: 0

Signals from the sea: the structural peculiarity of lipid A and weak immunostimulatory lipopolysaccharide from Rheinheimera japonica. 海洋信号：日本莱茵海参脂质A和弱免疫刺激脂多糖的结构特性。

IF 4.2

RSC Chemical Biology Pub Date : 2025-07-07 DOI: 10.1039/d5cb00134j

Stefania De Chiara, Francesca Olmeo, Emanuela Andretta, Luca De Simone Carone, Marcello Mercogliano, Vlada S Belova, Lyudmila A Romanenko, Maxim S Kokoulin, Alba Silipo, Antonio Molinaro, Flaviana Di Lorenzo

{"title":"Signals from the sea: the structural peculiarity of lipid A and weak immunostimulatory lipopolysaccharide from Rheinheimera japonica.","authors":"Stefania De Chiara, Francesca Olmeo, Emanuela Andretta, Luca De Simone Carone, Marcello Mercogliano, Vlada S Belova, Lyudmila A Romanenko, Maxim S Kokoulin, Alba Silipo, Antonio Molinaro, Flaviana Di Lorenzo","doi":"10.1039/d5cb00134j","DOIUrl":"10.1039/d5cb00134j","url":null,"abstract":"Lipopolysaccharides (LPSs) isolated from marine bacteria represent a valuable resource for biomedical innovation. Here, we report the first structural elucidation of the lipid A moiety and a preliminary immunological assessment of the full LPS from the marine Gram-negative Rheinheimera japonica KMM 9513T. Using MALDI-TOF mass spectrometry (MS) and tandem MS, we show that the lipid A from R. japonica KMM 9513T exhibits a heterogeneous architecture, composed of mono- and bis-phosphorylated tetra- and penta-acylated species with variations in the acyl chain length, saturation, branching, and positional isomerism. Functionally, the full LPS was found to be immunologically silent toward TLR4-mediated NF-κB activation in HEK-Blue™ hTLR4 cells and triggered only modest, dose-dependent responses in differentiated human THP-1 macrophages. Strikingly, the R. japonica LPS was able to antagonize E. coli LPS-induced TLR4 activation, even at low doses. Overall, this study uncovers a structurally and functionally atypical marine LPS with a dual profile, inactive towards TLR4 yet capable of modulating LPS-induced signaling. These findings offer a promising basis to consider R. japonica LPS as a source of structural inspiration for the design of synthetic derivatives with controlled immunological properties.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676018","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

Exploring the immunoproteasome's substrate preferences for improved hydrolysis and selectivity† 探索免疫蛋白酶体对改善水解和选择性的底物偏好。

IF 3.1

RSC Chemical Biology Pub Date : 2025-07-07 DOI: 10.1039/D5CB00114E

Christine S. Muli, Cody A. Loy and Darci J. Trader

{"title":"Exploring the immunoproteasome's substrate preferences for improved hydrolysis and selectivity†","authors":"Christine S. Muli, Cody A. Loy and Darci J. Trader","doi":"10.1039/D5CB00114E","DOIUrl":"10.1039/D5CB00114E","url":null,"abstract":"The proteasome is an integral macromolecular machine responsible for regulated protein degradation, and its barrel-like core particle (CP) hydrolyzes protein substrates into peptide fragments. A proteasome isoform that is expressed under conditions of inflammation is known as the immunoproteasome (iCP), which incorporates different catalytic subunits of altered cleavage specificities from the standard proteasome (sCP). Probes and inhibitors have been generated to study iCP activity and for therapeutics, respectively; recently, the iCP has been harnessed as a prodrug enzyme to release bioactive compounds selectively into iCP-expressing cells. iCP-targeting probes, prodrugs, and inhibitors are based on peptide recognition sequences and their favorable interactions within the iCP's substrate channel. To better understand what unnatural substrates the iCP can recognize, we synthesized peptide-conjugated substrates and applied them to a liquid chromatography-mass spectrometry (LC-MS) method after incubation with purified human iCP. Structure–activity relationships of unnatural peptide-conjugated substrates revealed modifications that improved substrate selectively for the iCP by more than 3-fold compared to the original scaffold. As such, this report will be helpful to guide future iCP-targeting probes, prodrugs, and inhibitor design.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1306-1312"},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601775","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