RSC Chemical Biology最新文献_第9页

Precursor gene engineering expands the loop region of the lasso peptide microcin J25. 前体基因工程扩展了套索肽微霉素J25的环区。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-02 eCollection Date: 2026-07-08 DOI: 10.1039/d6cb00126b

Hui-Ni Tan, Julian D Hegemann, Manuel Maestre-Reyna, John Chu

引用次数: 0

Exploring the GM-CSF histidine triad as a modulator of structure, molecular motion, and ligand binding. 探索GM-CSF组氨酸三联体作为结构、分子运动和配体结合的调节剂。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-01 eCollection Date: 2026-07-08 DOI: 10.1039/d6cb00019c

Jennifer Y Cui, Iz Varghese, Anna S Bock, Mariana Floody, Fuming Zhang, Brenda M Rubenstein, George P Lisi

{"title":"Exploring the GM-CSF histidine triad as a modulator of structure, molecular motion, and ligand binding.","authors":"Jennifer Y Cui, Iz Varghese, Anna S Bock, Mariana Floody, Fuming Zhang, Brenda M Rubenstein, George P Lisi","doi":"10.1039/d6cb00019c","DOIUrl":"10.1039/d6cb00019c","url":null,"abstract":"Granulocyte macrophage-colony stimulating factor (GM-CSF) is a cytokine that plays a role in immune modulation. Its expression is associated with a multitude of effects ranging from harmful, as in diseases such as rheumatoid arthritis and multiple sclerosis, to beneficial, as in the mitigation of type-1 diabetes and neutropenia. However, there is a large gap in knowledge explaining how GM-CSF toggles its structure for such physiological and pathological interactions. Our work describes an ongoing attempt to address this gap by focusing on a clustered histidine triad within α-helices near the N-terminus, which prior studies have suggested play a role in binding ligands at an acidic pH. While GM-CSF is known to be highly flexible at a more acidic pH, several properties of its histidine triad remain unclear at the physiological pH at which GM-CSF would encounter its binding partners. We describe an effort to characterize the role of the GM-CSF histidines under physiological pH, specifically to determine if these histidines are key to GM-CSF structural integrity, and whether individual histidine residues modulate binding as they do at a lower pH. Our findings reveal that, while the histidine residues have an impact on GM-CSF structure, flexibility, and stability, they alone do not modulate the affinity for ligands at neutral pH. These data provide an initial explanation for the pleiotropic functions and interactions of GM-CSF within a biophysical context.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1409-1419"},"PeriodicalIF":3.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200433","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

Synthesis and characterization of a novel phosphatidylinositol 5-phosphate (PI(5)P) photoaffinity probe. 新型5-磷酸磷脂酰肌醇（PI(5)P）光亲和探针的合成与表征。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-01 eCollection Date: 2026-07-08 DOI: 10.1039/d6cb00148c

Glen Brodie, Ahmed Sayed, Sarah Kreuz, Wolfgang Fischle, Stuart J Conway

{"title":"Synthesis and characterization of a novel phosphatidylinositol 5-phosphate (PI(5)P) photoaffinity probe.","authors":"Glen Brodie, Ahmed Sayed, Sarah Kreuz, Wolfgang Fischle, Stuart J Conway","doi":"10.1039/d6cb00148c","DOIUrl":"10.1039/d6cb00148c","url":null,"abstract":"Phosphatidylinositol 5-phosphate (PI(5)P) plays a crucial role in cellular signaling, cell proliferation, the DNA damage repair response, and gene transcription. However, the underlying mechanism of PI(5)P function in these cellular pathways is poorly understood. This lack of understanding results at least in part, from the dearth of available chemical tools to enable the investigation of PI(5)P interaction with target proteins in the corresponding biological systems. Here, we report the design and synthesis of a novel phosphatidylinositol 5-phosphate-based photoaffinity probe. The probe bound and photo-crosslinked to purified, recombinant hUHRF1 and TAF1 proteins that are known PI(5)P-interacting factors. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry with an azide-functionalized TAMRA dye allowed visualization of these proteins. We further show that the PI(5)P photoaffinity probe was functional in complex cell lysate by demonstrating protein crosslinking and fluorescent visualization with a TAMRA-azide. The data presented here validate the novel photoaffinity probe as a molecular tool for analyzing interactions and mapping the PI(5)P interactome.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1372-1381"},"PeriodicalIF":3.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151749","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

Real-time monitoring of glycocarrier formation unravels cryptic details in glycosyl transfer. 糖载体形成的实时监测揭示了糖基转移的神秘细节。

IF 3.9

RSC Chemical Biology Pub Date : 2026-06-01 eCollection Date: 2026-07-08 DOI: 10.1039/d6cb00069j

Ryan D Packer, Angelo Gallo, Alexander D Cameron, Somnath Mondal, Józef R Lewandowski, Manuela Tosin

引用次数: 0

Pharmacology of estrogen-related receptors (ERRs) agonists. 雌激素相关受体激动剂的药理学研究。

IF 3.9

RSC Chemical Biology Pub Date : 2026-05-29 eCollection Date: 2026-07-08 DOI: 10.1039/d6cb00077k

Mohamed O Radwan, Soumitra Guin, Thomas P Burris

{"title":"Pharmacology of estrogen-related receptors (ERRs) agonists.","authors":"Mohamed O Radwan, Soumitra Guin, Thomas P Burris","doi":"10.1039/d6cb00077k","DOIUrl":"10.1039/d6cb00077k","url":null,"abstract":"The estrogen-related receptors (ERRs) are a subfamily of orphan nuclear receptors that share high structural homology with classical estrogen receptors but do not bind endogenous estrogens. The three isoforms - ERRα, ERRβ, and ERRγ - exhibit constitutive transcriptional activity and regulate genes involved in mitochondrial biogenesis, oxidative metabolism, and energy homeostasis. ERRα and ERRγ are highly expressed in metabolically active tissues, including the heart, skeletal muscle, and liver, where they play central roles in metabolic adaptation and muscle function. Pharmacological activation of ERRα and ERRγ has therefore emerged as a promising strategy for the treatment of metabolic and muscle-related disorders as well as conditions where mitochondrial function decreases such as aging. This review focuses on the pharmacology of ERRs, their agonists, and the medicinal chemistry strategies underlying their development. Agonists are classified according to chemotype, and the structure-activity relationships (SAR) of each scaffold are analyzed, highlighting key pharmacological strengths and limitations. The chemotypes discussed include acyl hydrazones, 2,5-disubstituted thiophenes, pyrido[1,2-α]pyrimidin-4-ones, 1,2,3-triazoles, bisphenols, and amide-based agonists. Collectively, this work provides a comprehensive framework to guide the rational design of next generation ERRs agonists with improved pharmacological and translational potential.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1265-1277"},"PeriodicalIF":3.9,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13234766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200489","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

Tipping the balance: synthesis and evaluation of centrinone-based degraders of polo-like kinase 4. 打破平衡：马球样激酶4的中心醇基降解物的合成和评价。

IF 3.9

RSC Chemical Biology Pub Date : 2026-05-29 eCollection Date: 2026-07-08 DOI: 10.1039/d5cb00315f

Andrej Kovacevic, Aleksandar Salim, Crisálida Borges, Patrick Meraldi, Sascha Hoogendoorn

引用次数: 0

Protein digestion using a cysteine-specific backbone cleavage reagent. 用半胱氨酸特异性主干切割试剂进行蛋白质消化。

IF 3.9

RSC Chemical Biology Pub Date : 2026-05-28 eCollection Date: 2026-08-05 DOI: 10.1039/d6cb00152a

Yu-De Chuang, Tsung-Jung Yang, Yu-Chi Chih, Ya-Rong Chen, Po-Cheng Kuo, Cheng-Chih Hsu, Shao-Lun Chiou, John Chu

{"title":"Protein digestion using a cysteine-specific backbone cleavage reagent.","authors":"Yu-De Chuang, Tsung-Jung Yang, Yu-Chi Chih, Ya-Rong Chen, Po-Cheng Kuo, Cheng-Chih Hsu, Shao-Lun Chiou, John Chu","doi":"10.1039/d6cb00152a","DOIUrl":"10.1039/d6cb00152a","url":null,"abstract":"Mass spectrometry (MS)-based protein analysis is an indispensable tool in modern biomedical research. A key step in sample preparation is proteolytic digestion using enzymes with well-defined amino acid specificity, such as trypsin, chymotrypsin, and StaphV8 protease, which cleave at basic, aromatic, and acidic residues, respectively. The absence of cysteine (Cys)-specific cleavage methods is a gap in the current protein analysis toolbox. Herein, we report a chemical reagent (1) that selectively cleaves the N-terminal amide bond of Cys residues in proteins. Using glutathione as a model peptide, we investigated the reaction kinetics in detail and identified optimized conditions for protein cleavage. Using thioesterase as a model protein, we further demonstrated that 1 is fully compatible with modern MS-based proteomics workflows, including in-gel digestion, where it can be used in combination with existing proteases. This reaction proceeds rapidly and selectively in aqueous buffers, affording high yields while converting the reactive Cys side-chain thiol into a chemically inert five-membered heterocyclic moiety. This transformation eliminates the need for the commonly employed iodoacetamide capping step and introduces a distinct mass tag that facilitates downstream data analysis. Overall, these features establish 1 as a robust and practical new tool for protein analysis.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1568-1573"},"PeriodicalIF":3.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13306187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346678","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

The inhibitors of 17β-HSD10: are they any good? 17β-HSD10抑制剂：效果好吗？

IF 3.9

RSC Chemical Biology Pub Date : 2026-05-28 eCollection Date: 2026-07-08 DOI: 10.1039/d6cb00093b

Ernst Kwa, Charlene E Ogilvie, Natalie C Kormos, Alison J E Green, Terry K Smith, Frank J Gunn-Moore

{"title":"The inhibitors of 17β-HSD10: are they any good?","authors":"Ernst Kwa, Charlene E Ogilvie, Natalie C Kormos, Alison J E Green, Terry K Smith, Frank J Gunn-Moore","doi":"10.1039/d6cb00093b","DOIUrl":"10.1039/d6cb00093b","url":null,"abstract":"The advent of the first disease-modifying therapies for Alzheimer's disease (AD) has renewed optimism for effective prevention and treatment strategies. Growing mechanistic insights indicate that AD pathogenesis is multifactorial and non-linear, better conceptualized as a circular vortex in which interconnected pathological processes reinforce one another. This complexity highlights the necessity for multiple druggable targets and combination-based therapeutic approaches. A hallmark of AD is reduced cerebral glucose utilization, revealed by positron emission tomography studies, reflecting profound metabolic disruption and mitochondrial dysfunction. Among mitochondrial candidates, 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10), encoded by HSD17B10, has emerged as a protein of interest. Despite debate surrounding its substrate specificity due to conflicting in vitro data, its elevated expression in neurons and astrocytes within AD brains underscores its potential relevance. This review outlines chemical entities targeting both catalytic and non-catalytic functions of 17β-HSD10 and examines whether its inhibition offers biological efficacy and clarifies its metabolic roles in the living brain.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1278-1295"},"PeriodicalIF":3.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228653","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 two-step bioconjugation of S. aureus lipoteichoic acid (LTA) affords fluorescent probes that illuminate the interaction between Gram-positive glycolipids and mammalian cell membranes. 金黄色葡萄球菌脂质胆酸（LTA）的两步生物偶联提供了荧光探针，阐明革兰氏阳性糖脂与哺乳动物细胞膜之间的相互作用。

IF 3.9

RSC Chemical Biology Pub Date : 2026-05-26 eCollection Date: 2026-07-08 DOI: 10.1039/d6cb00113k

Jake Henry, Joe Nabarro, Harriet Chidwick, Georgia Conrich-Wilks, Emily G Morton-West, Alice Crook, Dave Boucher, Nathalie Signoret, Martin A Fascione

{"title":"A two-step bioconjugation of S. aureus lipoteichoic acid (LTA) affords fluorescent probes that illuminate the interaction between Gram-positive glycolipids and mammalian cell membranes.","authors":"Jake Henry, Joe Nabarro, Harriet Chidwick, Georgia Conrich-Wilks, Emily G Morton-West, Alice Crook, Dave Boucher, Nathalie Signoret, Martin A Fascione","doi":"10.1039/d6cb00113k","DOIUrl":"10.1039/d6cb00113k","url":null,"abstract":"Lipoteichoic acid (LTA), a major constituent of Gram-positive bacteria cell wall, is an amphiphilic glycolipid and well-established stimulator of immune cells through activation of Toll-Like Receptor 2 (TLR2) complexes. LTA binding to TLR2 is essential for this process but not the only step required, meaning that new tools are needed to visualize and track LTA interactions with host cells. Here we present a simple aldehyde-based bioconjugation approach to label native LTA purified from S. aureus, generating fluorescent LTA derivatives with minimal functional impairment by targeting modification distal to the diacylglycerol lipid anchor that is essential for host cell interactions. We demonstrate that this approach not only facilitates the study of fluorescent LTA binding to established host TLRs, but also reveals an underappreciated propensity of LTA lipids to interact with mammalian membranes independently of TLRs.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1402-1408"},"PeriodicalIF":3.9,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13231905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164972","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

Minimal N-methylated and stapled peptide inhibitors of the autophagy protein GABARAP. 自噬蛋白GABARAP的最小n -甲基化和钉状肽抑制剂。

IF 3.9

RSC Chemical Biology Pub Date : 2026-05-26 eCollection Date: 2026-07-08 DOI: 10.1039/d6cb00111d

Imani McDonald, Joana A Wilms, Nicholas Cardi, Alexander Engstrom, Jiayuan Miao, Dieter Willbold, Yu-Shan Lin, R Scott Lokey, Oliver H Weiergräber, Joshua A Kritzer

{"title":"Minimal N-methylated and stapled peptide inhibitors of the autophagy protein GABARAP.","authors":"Imani McDonald, Joana A Wilms, Nicholas Cardi, Alexander Engstrom, Jiayuan Miao, Dieter Willbold, Yu-Shan Lin, R Scott Lokey, Oliver H Weiergräber, Joshua A Kritzer","doi":"10.1039/d6cb00111d","DOIUrl":"10.1039/d6cb00111d","url":null,"abstract":"The LC3/GABARAP protein family is a promising target for selective inhibition of autophagy. Further, LC3/GABARAP ligands have been used as targeted degraders of soluble proteins, protein aggregates, mitochondria, lipid droplets, and RNA. However, the small molecules used for such applications have poor binding affinity and known off-target effects. LC3/GABARAP proteins are challenging targets for small-molecule drug development due to their long, shallow binding grooves. In this work, we evaluate multiple approaches to stabilizing the extended structure of the native binding motif, producing N-methylated peptides and stapled peptides with low nanomolar affinity. A crystal structure and molecular dynamics simulations support a model where the N-methylation pre-organizes the motif into an extended, strand-like structure. N-Methylation allowed minimization of the binding motif to a tetrapeptide that retained sub-micromolar affinity while minimizing charge and overall molecular weight. The truncated, N-methylated tetrapeptide showed passive permeability in artificial membrane and cell-based transwell assays. These results highlight new drug-like space for LC3/GABARAP ligands with high affinity and subfamily selectivity.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1319-1329"},"PeriodicalIF":3.9,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13234858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200572","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