RSC Chemical Biology最新文献

{"title":"Visualizing stress granule dynamics with an RNA guanine quadruplex targeted ruthenium(ii) peptide conjugate†","authors":"Rhianne C. Curley, Lorcan Holden and Tia E. Keyes","doi":"10.1039/D5CB00008D","DOIUrl":"10.1039/D5CB00008D","url":null,"abstract":"<p >Stress granules (SGs) are membraneless ribonucleoprotein assemblies that form in response to cellular stress. They have been linked to cell survival and cancer progression, though many questions remain regarding their structure, function and therapeutic potential. Live-cell fluorescence imaging is key to advancing understanding of SGs, but there are very few small-molecule probes reported that selectively image these organelles. RNA G-quadruplex (rG4) folding is believed to play a role in initiation of SG formation. Thus, to create a probe for SGs, we conjugated a G4 binding domain peptide from RNA helicase associated with AU-rich element (RHAU) to a luminescent [Ru(bpy)<small>₂</small>(PIC-COOH)]<small>²⁺</small>, Ru-RHAU. Ru-RHAU is designed to target rG4s and thus SGs in live cells. Studies <em>in cellulo</em> demonstrate that Ru-RHAU can induce SG formation in a concentration and time dependent manner and immunolabelling confirmed the complex remains associated with rG4s in the SGs. The SG stimulation is attributed to stabilization of rG4 by Ru-RHAU consistent with rG4's role in SG formation. Ru-RHAU shows low cytotoxicity under imaging conditions, facilitating prolonged observation in live cells. Interestingly, under more intense photoirradiation, Ru-RHAU induces phototoxicity through an apoptotic pathway. Ru-RHAU is a versatile tool for probing SG dynamics and function in cellular stress responses and has heretofore unconsidered potential in phototherapeutic applications targeting SGs.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 9","pages":" 1403-1413"},"PeriodicalIF":3.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508788","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}

{"title":"Advances in programmable DNA nanostructures enabling stimuli-responsive drug delivery and multimodal biosensing","authors":"Yao Hong, Wenyue Ma, Meixia Wang and Hong-Hui Wang","doi":"10.1039/D5CB00057B","DOIUrl":"10.1039/D5CB00057B","url":null,"abstract":"<p >Recent advancements in DNA nanotechnology have unlocked unprecedented opportunities to address critical challenges in precision medicine, particularly in targeted drug delivery and biomedical imaging. Conventional nanocarriers often suffer from poor spatiotemporal control, suboptimal tumor accumulation, and non-specific biodistribution. To overcome these limitations, DNA-engineered nanostructures—including tile-based assemblies, origami frameworks, spherical nucleic acids, and stimuli-responsive hydrogels—have emerged as programmable platforms capable of dynamically responding to tumor microenvironmental cues (<em>e.g.</em>, pH, enzymatic activity, redox gradients) for triggered drug release. In this review, we comprehensively analyze these architectures with emphasis on their modular design strategies, <em>in vivo</em> stability improvements <em>via</em> polyethylene glycol (PEG) functionalization, and multi-ligand targeting capabilities against cancer-specific biomarkers. In addition to therapeutic uses, these nanostructures also enable highly sensitive detection of circulating tumor DNA and exosomes using fluorescence resonance energy transfer (FRET) probes, electrochemiluminescence amplification circuits, SERS substrates, and cell variable region sensing technology. They also allow for real-time monitoring of dynamic intercellular interactions, overcoming the constraints of traditional sensing methods. This review systematically elaborates on the structural characteristics of DNA assemblies and summarizes the innovative applications of these nanostructures in multimodal detection, offering a more comprehensive perspective for early cancer diagnosis and precision treatment. Despite promising preclinical results, key translational challenges persist, including scalable manufacturing bottlenecks, immune compatibility optimization, and rigorous assessment of long-term nanotoxicity. Future integration with artificial intelligence-driven design tools may catalyze the development of next-generation theranostic nanodevices, ultimately bridging the gap between synthetic biology and clinical oncology.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 9","pages":" 1366-1385"},"PeriodicalIF":3.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530222","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}

{"title":"Quantitative neuropeptide analysis by mass spectrometry: advancing methodologies for biological discovery","authors":"Angel Erbey Ibarra, Wenxin Wu, Haoran Zhang and Lingjun Li","doi":"10.1039/D5CB00082C","DOIUrl":"10.1039/D5CB00082C","url":null,"abstract":"<p >Neuropeptides are critical endogenous signaling molecules involved in a wide range of biological processes, including neurotransmission, hormonal regulation, immune responses, and stress management. Despite their importance, the field of neuropeptide research has been historically hampered by significant technical challenges. These include their low abundance in biological systems, diverse and complex post-translational modifications, dynamic expression patterns, and susceptibility to degradation. As such, traditional proteomics approaches often fall short of accurately characterizing neuropeptides, underscoring the need for specialized methodologies to unlock their biological and translational potential. This review evaluates state-of-the-art quantitative mass spectrometry (MS)-based peptidomics, emphasizing their impact on neuropeptide analysis. We highlight how strategies in label-free and label-based quantitation, tandem MS acquisition, and mass spectrometry imaging provide unprecedented sensitivity and throughput for capturing the landscape of neuropeptides and their modifications. Importantly, the review bridges technological innovation with practical applications, highlighting how these approaches have been utilized to uncover novel neuropeptides and elucidate their roles in systems biology and disease pathways.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1214-1232"},"PeriodicalIF":3.1,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318303","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}

{"title":"Correction: Proximity-induced SuFEx increases the potency of cytosolic nucleotidase inhibitors and reveals a rare example of covalently targeted histidine","authors":"Mikolaj Chrominski, Marcin Warminski, Mateusz Kozarski, Dorota Kubacka, Joanna Panecka-Hofman, Tomasz Spiewla, Mikolaj Zmudzinski, Jacek Jemielity and Joanna Kowalska","doi":"10.1039/D5CB90025E","DOIUrl":"10.1039/D5CB90025E","url":null,"abstract":"<p >Correction for ‘Proximity-induced SuFEx increases the potency of cytosolic nucleotidase inhibitors and reveals a rare example of covalently targeted histidine’ by Mikolaj Chrominski <em>et al.</em>, <em>RSC Chem. Biol.</em>, 2025, <strong>6</strong>, 942–947, https://doi.org/10.1039/d5cb00005j.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1184-1184"},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303153","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}

{"title":"Emerging gut microbial glycoside hydrolase inhibitors","authors":"Mark E. Kowalewski and Matthew R. Redinbo","doi":"10.1039/D5CB00050E","DOIUrl":"10.1039/D5CB00050E","url":null,"abstract":"<p >The human gut microbiota has been linked to numerous diseases through their metabolism of molecules in the gastrointestinal tract. Post-translational glycosylation is applied to many secreted proteins, including mucins and immunoglobulins, and glycosides are present in diet and generated by host metabolism systems. Thus, glycosides are key targets for degradation by gut microbial glycoside hydrolases (GHs). Indeed, diverse xenobiotic compounds, including therapeutics and dietary phytochemicals, along with endobiotics like neurotransmitters and hormones, are conjugated to monosaccharides making them substrates for GH enzymes. A range of GH inhibitors have been developed to study lysosomal storage diseases, treat viral infections, and to address type II diabetes. Recently, GH inhibitors have offered promising avenues for investigating gut microbial GHs and their influence on host health and disease. In this review we describe the growing classes of GH inhibitors and their applications in studying gut microbial GHs that target host-derived glycans and dietary and drug-xenobiotic molecules. We also review the use of GH-targeting activity-based probes to pinpoint specific proteins expressed by the gut microbiota that influence molecular and phenotypic outcomes. As we deepen our understanding of gut microbial GH function, we will further elucidate the roles played by the microbiota in host physiology and disease toward potential therapeutic interventions that target non-host factors in acute and chronic disorders.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1233-1251"},"PeriodicalIF":3.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327167","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}

{"title":"Regulation of carcinogenesis through multiple zinc fingers in ZBTB20†","authors":"Hyunyong Kim, Yunha Hwang, Jin Sung Cheong and Seung Jae Lee","doi":"10.1039/D5CB00088B","DOIUrl":"10.1039/D5CB00088B","url":null,"abstract":"<p >Zinc finger (ZF) proteins regulate transcription by interacting with <em>cis</em>-acting elements for gene expression in response to stimuli within physiological systems. Bioinformatic studies have proposed that zinc finger and BTB (Broad complex, Tramtrack, Bric-à-brac) domain-containing protein 20 (ZBTB20) acts as a key regulator of crucial genes associated with carcinogenesis. However, biochemical experiments using purified proteins remain unreported. In this study, we investigated the regulatory functions of the ZF domains in ZBTB20, which has five CX<small>₂</small>CX<small>₁₂</small>HX<small>₃</small>H-type classical ZF domains, in the inhibition and expression of downstream transcription factors, including alpha-fetoprotein (AFP) and forkhead box transcription factor O1 (FOXO1). The four ZF domains of ZBTB20, ZBTB20(ZF1-4), inhibit the expression of AFP with specificity (<em>K</em><small>_d</small> = 0.6 ± 0.04 nM) by interacting with the <em>afp</em> promoter (5′-ACCTA). Furthermore, ZBTB20(ZF1-4) or ZBTB20(ZF1-5) inhibited the expression of FOXO1, thereby suppressing cell cycle arrest and inducing tumorigenesis by binding to the promoter of <em>foxO1</em> (5′-ACCGCCGCCTC) with affinities of 1.7 ± 0.07 and 2.1 ± 0.05 nM, respectively. The results provide the first evidence that ZBTB20 regulates gene expression through ZF domains positioned at the C-terminus through interactions with <em>cis</em>-acting elements to achieve specificity and selectivity. The balance of ZBTB20 expression can be a crucial issue for the regulation of two downstream transcription factors to maintain homeostasis.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1165-1173"},"PeriodicalIF":4.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267566","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}

{"title":"Metal-mediated peptide processing. How copper and iron catalyze diverse peptide modifications such as amidation and crosslinking","authors":"Ninian J. Blackburn","doi":"10.1039/D5CB00085H","DOIUrl":"10.1039/D5CB00085H","url":null,"abstract":"<p >Peptide processing is an important post-translational function that converts newly synthesized pro-peptides into their biologically active mature forms. In this review we discuss two such processes, peptide amidation and ribosomally synthesized post-translationally modified peptide (RiPP) synthesis. The first step in peptide amidation is catalyzed by copper, utilizing a single enzyme peptidylglycine monooxygenase (PHM), while RiPP chemistry can utilize Fe-containing radical SAM enzymes and in a more recent discovery Cu-containing burpitide cyclases. For PHM we describe the canonical mechanism built on three decades of structural, spectroscopic and computational work that posits mononuclear reactivity coupled to long range electron transfer. We discuss this alongside new experimental evidence that suggests instead an open-to-closed conformationally gated mechanism where a binuclear copper entity is the reactive species. Next we describe new insights into RiPP chemistry of thioether formation formed <em>via</em> cysteine to peptidyl-C crosslinking in the radical SAM enzymes PapB and Tte1186. Here Se edge XAS has documented selenocysteine to Fe binding at an auxiliary FeS cluster as an important step in S/Se to peptidyl-C coupling. Finally we examine analogous radical-induced peptide crosslinking in a new class of peptide cyclases termed burpitide cyclases (BpCs) some of which exhibit a striking similarity to PHM, yet show catalytic chemistry leading to a different product profile. These comparisons emphasize how nature leverages very specific properties of metal ions, and their ability to underpin catalysis <em>via</em> radical processes to bring about a variety of important biochemical and biological outcomes.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1048-1067"},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303119","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}

{"title":"trans-Cyclooctene-caged-IL-1β immunocytokine-constructs ligated to unmodified nanobodies allow click-2-release-based control of cytokine activity†","authors":"Amber Barendrecht, Heleen H. C. Peeters, Diana Torres-García, M. Thierry Shema, Alexi J. C. Sarris, Shimrit David, Göktuğ Aba, Camille M. Le Gall, Martin Wilkovitsch, Martijn Verdoes, Hannes Mikula, Mark A. Travis and Sander I. van Kasteren","doi":"10.1039/D5CB00113G","DOIUrl":"10.1039/D5CB00113G","url":null,"abstract":"<p >Immunocytokines have emerged as a promising modality in cancer therapy, capitalizing on the precision of antibodies to deliver cytokines selectively to tumours. Yet, the toxicity of the cytokine portion of these antibody-cytokine constructs remains a major dose-limiting issue. We present a new approach to control cytokine function without affecting binding of the targeting moiety. By modifying the cytokine with <em>trans</em>-cyclooctene carbamates at the lysine positions, we can reduce the binding to the receptor of various highly pro-inflammatory cytokines. Then, using a click-2-release (C2R)-approach, we can reactivate the cytokine activity by reacting it with a variety of tetrazines, through a Diels–Alder-pyridazine-elimination cascade. Finally, we show that the caged cytokines can be conjugated <em>via</em> a sortase motif to an unmodified targeting nanobody resulting in a targetable caged immunocytokine construct.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1068-1078"},"PeriodicalIF":4.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276222","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}

{"title":"Exploring marine glycans: structure, function, and the frontier of chemical synthesis","authors":"Sandhya Mardhekar, Phuong Luong and Peter H. Seeberger","doi":"10.1039/D5CB00090D","DOIUrl":"10.1039/D5CB00090D","url":null,"abstract":"<p >Marine glycans are structurally diverse biomolecules that play pivotal roles in oceanic carbon cycling by regulating microbial metabolism, accelerating organic matter turnover, and contribute to carbon sequestration. Glycans originating from marine organisms exhibit a wide range of bioactivities and applications in medicine, biotechnology, cosmetics, food and agriculture. The structural complexity of glycans poses significant challenges in understanding their functions, as traditional purification and characterization methods are often hindered by their inherent heterogeneity. To overcome these challenges, enzymatic extraction using glycoside hydrolases and carbohydrate-active enzymes (CAZymes) enables the selective recovery of native glycans, while automated glycan assembly (AGA) provides a robust approach for the rapid and reproducible synthesis of structurally defined glycans. Subjecting synthetic glycans to enzymatic degradation enables researchers to explore the inverse relationship between glycan complexity and microbial degradation, suggesting that algae can generate complex glycans at a rate exceeding bacterial decomposition, thereby reinforcing carbon storage. Here, we present a comprehensive overview of marine glycan sources and their structural diversity. We highlight the importance of employing two complementary methods, enzymatic extraction as a critical tool for glycan identification and AGA as an advanced synthetic platform, to build a refined framework for elucidating the ecological role and industrial potential of marine glycans.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 8","pages":" 1195-1213"},"PeriodicalIF":3.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327168","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}

{"title":"Biochemical characterization of Bifidobacterium bifidum peptidoglycan d,l-endopeptidase BbMep that generates NOD2 ligands†","authors":"Jeric Mun Chung Kwan, Shiliu Feng, Evan Wei Long Ng and Yuan Qiao","doi":"10.1039/D5CB00086F","DOIUrl":"10.1039/D5CB00086F","url":null,"abstract":"<p >Soluble peptidoglycan fragments produced by the gut bacteria are key effectors in microbiota–host crosstalk. Here, we biochemically characterized BbMep, an NlpC/p60 domain-containing peptidoglycan <small>D</small>,<small>L</small>-endopeptidase from <em>Bifidobacterium bifidum</em>, which efficiently digests Lys- or Orn-type sacculi. Digestion of human stool-derived muropeptides by BbMep enhances NOD2 activation.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" 7","pages":" 1174-1183"},"PeriodicalIF":4.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303152","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}