RSC Chemical Biology最新文献

{"title":"The structural chemistry and biosynthesis of chlorophylls.","authors":"C Neil Hunter, Felix S Morey-Burrows","doi":"10.1039/d6cb00082g","DOIUrl":"10.1039/d6cb00082g","url":null,"abstract":"<p><p>Chlorophylls (Chls) harvest the solar energy that drives photosynthesis, which underpins most of the food chains on our planet. Starting from protoporphyrin IX, just seven biosynthetic reactions culminate in the synthesis of Chl <i>a</i>, the major light-absorbing pigment on Earth. Other such pigments, Chls <i>b</i>, <i>c</i>, <i>d</i> and <i>f</i>, widen the absorption range in the visible and red regions of the spectrum, and several bacteriochlorophylls (BChls), BChls <i>a</i>, <i>b</i> and <i>g</i> in particular, open new spectral windows allowing organisms to harvest near infra-red light. This perspective surveys the structural features of porphyrins, chlorins and bacteriochlorins that impart their characteristic absorption features, then presents a similar analysis of the biosynthetic intermediates leading to Chls <i>a</i>, <i>b</i>, <i>c</i>, <i>d</i> and <i>f</i>. The interlinked Chl and BChl biosynthetic pathways are summarised, then the rest of the perspective focusses on the enzymes that synthesise Chls <i>a</i>, <i>b</i>, <i>c</i>, <i>d</i> and <i>f</i>. AlphaFold 3 was used to model a complete set of structures for Chl biosynthesis enzymes, predicting intersubunit associations and the arrangements of cofactors and bound substrates, and providing insights into catalytic mechanisms. A new scheme for binding substrates and transferring products between pathway enzymes suggests how synthetic biology approaches can assemble hybrid Chl and BChl pathways to expand the spectral range for harvesting and using solar energy.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1134-1166"},"PeriodicalIF":3.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13297055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346667","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 monitoring mammalian circadian components and their rhythms using reporter systems.","authors":"Bhavna Kalyanaraman, Emmanuel F Rivera-Iglesias, Michelle E Farkas","doi":"10.1039/d5cb00332f","DOIUrl":"10.1039/d5cb00332f","url":null,"abstract":"<p><p>Circadian rhythms are innate biological processes that cycle over periods of approximately 24 hours and are crucial in regulating many physiological and metabolic functions. At the molecular level in mammals, these cell-autonomous oscillations are controlled by a network of self-regulating feedback loops comprised of transcriptional and translational regulators. Reporter platforms for following promoter activity and/or proteins <i>via</i> detectable fluorescent and bioluminescent entities have facilitated the tracking of circadian elements in cells and organisms in real-time, which is especially important for studying such a dynamic biological system. As a result, reporters have been pivotal in uncovering fundamental aspects of the molecular core clock, changes in individual components in healthy <i>versus</i> various disease models, and screening for synthetic clock modulators. While the initially established tools of <i>in vivo</i> reporters (<i>i.e.</i>, Per2::Luc mice) continue to be widely utilized, newer ones have capabilities for evaluating other components and performing simultaneous assessments of multiple circadian components across different levels of expression. Concurrently, <i>in vitro</i> reporter models have been developed to track alterations in rhythms and protein presence in various cellular models, including those of disease. In this review, we discuss various reporter systems, including historical context, and their applications for monitoring rhythms at transcriptional and translational levels of expression, <i>in vitro</i> and <i>in</i>/<i>ex vivo</i>, with a focus on mammalian systems. Furthermore, we assess the advantages, disadvantages, and limitations of employing bioluminescent and fluorescent reporters in monitoring biological rhythms and components. Our goals are to provide an account of available reporter systems and pose considerations for their use and the development of technologies that can be used to expand our tracking and understanding of the molecular clock.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1687-1702"},"PeriodicalIF":3.9,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13358711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438209","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":"Sydnone-modified nucleosides as versatile tools for bioorthogonal post-synthetic functionalization of antisense oligonucleotides.","authors":"Alexandra Bristiel, Alexandre Khuu, Mathilde Poulet, Frédéric Taran, Dominique Urban, Raphaël Guignard, Dominique Guianvarc'h","doi":"10.1039/d6cb00100a","DOIUrl":"10.1039/d6cb00100a","url":null,"abstract":"<p><p>The development of efficient bioconjugation methods is essential for enhancing the therapeutic potential of oligonucleotides, especially antisense oligonucleotides (ASOs). Two main strategies are used for modification during oligonucleotide solid-phase synthesis: the early incorporation of functionalized monomers, or the post-synthetic modification of precursors bearing small reactive groups-the latter offering greater versatility and yield. Extensive efforts have been dedicated to incorporating bioorthogonal groups into phosphoramidite building blocks to enable the controlled chemical synthesis of reactive oligonucleotides suitable for post-synthetic modifications. Among these, alkynes and cyclooctynes are the most widely used, enabling Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) and strain-promoted azide-alkyne cycloaddition (SPAAC), respectively. We recently demonstrated the compatibility of the sydnone group with automated solid-phase chemistry. This chemical motif shows significant promise in oligonucleotide chemistry, as it allows for strain-promoted sydnone-alkyne cycloaddition (SPSAC), a reaction that has recently emerged as an efficient alternative to SPAAC for cellular studies. Herein, we present the synthesis of three sydnone-functionalized phosphoramidite monomers, their incorporation into ASOs, and an evaluation of their chemical and biological properties. These developments aim to expand the bioconjugation toolbox for ASO tracking, targeting, and imaging, thereby improving their therapeutic application and the understanding of intracellular mechanisms.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"2059-2068"},"PeriodicalIF":3.9,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798966","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":"Discovery and characterization of a novel class of cyclic peptidic compounds inhibiting the subunit interaction of the protein kinase CK2α₂β₂ holoenzyme.","authors":"Christian Werner, Sophia Eimermacher, Miriam Lauwers, Dirk Lindenblatt, Esra Seymen, Ekaterina Kulko, Leonard Klein, Michaela Steinkrüger, Robin Baumann, Sarah Salamon, Cora Fried, Dietmar Fischer, Andreas Oder, Martin Neuenschwander, Claudia Götz, Karsten Niefind, Markus Pietsch","doi":"10.1039/d6cb00095a","DOIUrl":"10.1039/d6cb00095a","url":null,"abstract":"<p><p>CK2 belongs to the eukaryotic protein kinase superfamily and has a distinctive heterotetrameric quaternary structure. In the so-called CK2α₂β₂ holoenzyme, which is the main form of CK2 in human cells, two catalytic subunits (CK2α) are attached to a stable homodimer of non-catalytic subunits (CK2β). Most CK2 inhibitors described so far are ATP-competitive. Some of them are the subject of clinical studies because the enzyme is upregulated in many tumours, and CK2 activity contributes to tumour survival. An unconventional method to interfere with CK2 is to disturb the CK2α/CK2β interaction with small molecules. In a high-throughput screen against a 67 000-compound library using a fluorescence anisotropy-based displacement assay, we identified a group of derivatised cyclic pentapeptides that target the CK2β binding site of CK2α. The CK2β-competitive effect of these screening hits was verified using either human CK2α or its paralogous isoenzyme CK2α' as interaction partners. To this end, novel Förster resonance energy transfer-based CK2α/CK2β and CK2α'/CK2β interaction assays were developed and extensively tested. A result of these validation measurements was that the CK2β-antagonists bind more strongly to CK2α than to CK2α' although both paralogs do not differ in the amino acid composition at their CK2β interfaces. Co-crystallisation experiments of two high-affinity binders with CK2α and CK2α' led to three complex structures that confirm the binding of the compounds to the CK2β interface. The structures suggest a critical role of the β4β5-loop for the higher affinity of the compounds to CK2α compared to CK2α'. Furthermore, they offer suggestions on how to enhance their efficacy in the future.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1730-1742"},"PeriodicalIF":3.9,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148425165","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":"Probing sulfotransferase binding and inhibition with synthetic PAPS analogs reveals the role of the 3'-phosphate and informs molecular tool design.","authors":"Maria Matveeva, Agnieszka Młynarska-Cieślak, Mikołaj Chromiński, Tomasz Spiewla, Jonathan W Mueller, Jacek Jemielity, Joanna Kowalska","doi":"10.1039/d6cb00094k","DOIUrl":"10.1039/d6cb00094k","url":null,"abstract":"<p><p>Sulfotransferases (STs) are a class of enzymes that catalyze the transfer of the sulfuryl group (-SO₃ ^-), most commonly from the universal cofactor 3'-phosphoadenosine 5'-phosphosulfate (PAPS), to nucleophilic acceptors bearing hydroxyl or amino groups. Although this process is widespread in biology, it involves the energy-intensive synthesis of PAPS and the generation of a natural inhibitor of sulfotransferases - the bis-phosphorylated nucleotide 3'-phosphoadenosine 5'-phosphate (PAP). This study aims to provide a deeper insight into the structure-activity relationship of the PAPS-ST interaction and lay the groundwork for PAPS-derived molecular tool design. To this end, we report a library of chemically modified PAPS and PAP analogs and evaluate their binding and inhibitory properties toward the plant sulfotransferase AtSOT18 and mammalian SULT1A3. Using microscale thermophoresis, it was found that STs do not differentiate between the 5'-phosphosulfate and 5'-diphosphate analogs, making the latter non-functional mimics potentially useful for structural studies and revealing an important role of the 3'-phosphate in ligand recognition and binding specificity. The modifications at the 2'-, 5'-sites, or at the N6 and C8 positions of the adenine rarely made significant contributions to the stabilization of the complex. A strong preference for the adenine base over alternative nitrogenous bases in the cofactor structure was, however, observed. The use of ¹⁹F NMR spectroscopy as a molecular tool for screening potential inhibitors of AtSOT18 and SULT1A3 highlighted C8-(1-amino-2-azidoethyl)-substituted analogs as promising compounds for targeting STs. Overall, the study revealed several novel aspects of molecular recognition of PAPS by STs and laid the groundwork for future molecular tool design.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1650-1658"},"PeriodicalIF":3.9,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370160","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":"Probing the <i>C</i> ₃ symmetry of gramicidin S.","authors":"Alex Hoose, Javier Garcia-Ruiz, Ciara C M Lally, Camilla Dondi, Maxim G Ryadnov","doi":"10.1039/d6cb00134c","DOIUrl":"10.1039/d6cb00134c","url":null,"abstract":"<p><p>Gramicidin S continues to inspire antibiotic designs. It exhibits a conserved two-fold (<i>C</i> ₂) symmetry postulated to underpin its biological activity. Here we probe the <i>C</i> ₃ symmetry of gramicidin S and its impact on the folding and antibacterial properties of this antibiotic.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1546-1552"},"PeriodicalIF":3.9,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13307312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346703","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":"Cellular engagement of the SARS-CoV-2 macrodomain by GS-441524 and enhanced <i>in vitro</i> inhibition by its diphosphorylated metabolite.","authors":"Banhi Biswas, Junlin Zhuo, Jürgen Bosch, Hien Vu, Lorencia Pak, Rameez Raja, Anuradha Roy, Alessandro Panattoni, Michal Maryska, Petr Slavik, Kryštof Šigut, Anthony R Fehr, Rachy Abraham, Barbara S Slusher, Takashi Tsukamoto, Anthony K L Leung","doi":"10.1039/d6cb00139d","DOIUrl":"10.1039/d6cb00139d","url":null,"abstract":"<p><p>Coronavirus macrodomains (Mac1) counter host immunity by removing ADP-ribose. GS-441524, the parent nucleoside of remdesivir, inhibits SARS-CoV-2 Mac1, but its active metabolite and cellular engagement were undefined. GS-441524 selectively inhibits SARS-CoV-2 Mac1 over human MacroD2, engages Mac1 in cells but not MERS-CoV Mac1, with its diphosphate metabolite being most potent.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1559-1567"},"PeriodicalIF":3.9,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346530","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":"Engineering a light-controllable fluorescent protein for peroxynitrite detection <i>via</i> genetic code expansion.","authors":"Gloricelly M Roman Arocho, Parthasarathi Das, Sachin C Tennakoon, Jared B Shaw, Wei Niu, Jiantao Guo","doi":"10.1039/d6cb00083e","DOIUrl":"10.1039/d6cb00083e","url":null,"abstract":"<p><p>We report a noncanonical amino acid-containing photoconvertible fluorescent protein for selective peroxynitrite detection. Incorporation of <i>p</i>-borono-l-phenylalanine into circularly permuted mEos2 affords a peroxynitrite-responsive sensor that retains photoconversion capability, expanding chemical diversity in light-controllable fluorescent proteins.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1574-1577"},"PeriodicalIF":3.9,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13306567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346601","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":"Reversible formation of <i>S</i>-d-3-phosphoglyceroyl glutathione contributes to cellular protection from acylation by cyclic 3-phosphoglyceric anhydride.","authors":"Adilkhan Yeskendir, Adilet Bekmagambetov, Evelina Shkraba, Zariat Shatkenova, Zhanpeis Issayev, Aizhan Akhmadi, Dos D Sarbassov, Darkhan Utepbergenov","doi":"10.1039/d6cb00085a","DOIUrl":"10.1039/d6cb00085a","url":null,"abstract":"<p><p>A spontaneous cyclization of 1,3-bisphosphoglycerate produces a highly reactive cyclic 3-phosphoglyceric anhydride (cPGA), which damages cellular nucleophiles through indiscriminate acylation. Although evidence suggests that most of the cPGA is inactivated by DJ-1, a highly efficient cPGA hydrolase, alternative routes of cPGA detoxification have not been explored. Here, we use a kinetic approach to show that a thiol group of glutathione (GSH) reacts with cPGA to produce the corresponding thioester <i>S</i>-d-3-phosphoglyceroyl glutathione (pgGS). We found that pgGS is unstable and decomposes back to GSH and cPGA with a half-life of 80 minutes providing DJ-1 with another chance to inactivate cPGA. Apart from spontaneous decomposition, pgGS is efficiently hydrolyzed by Glyoxalase II (GlxII); therefore a significant fraction of cPGA that escapes hydrolysis by DJ-1 is trapped by GSH and subsequently detoxified. Experiments with DJ-1-null cells revealed that depletion of GSH causes a multi-fold increase in the cellular level of <i>N</i>-glyceroyl glutamine, confirming that reversible formation of pgGS in reaction of cPGA with GSH serves as a second line of defense against acylation of biomolecules by cPGA.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1632-1641"},"PeriodicalIF":3.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13273730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148279214","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":"Recent advances in near-infrared dye conjugates for near-infrared photoimmunotherapy (NIR-PIT): enhancing therapeutic efficacy and immune mechanisms.","authors":"Yoshikazu Fuse, Eita Sasaki, Orie Takayama, Sota Yamada, Kenjiro Hanaoka","doi":"10.1039/d6cb00132g","DOIUrl":"10.1039/d6cb00132g","url":null,"abstract":"<p><p>Near-infrared photoimmunotherapy (NIR-PIT) is an innovative cancer treatment modality that was approved in Japan in 2020 for the treatment of unresectable locally advanced or locally recurrent head and neck cancer. This therapy uses an antibody-dye conjugate (Ab-IR700), which consists of a monoclonal antibody targeting a specific cell-surface antigen and a phthalocyanine-based near-infrared dye, IR700, that functions as a photosensitizer. After selective accumulation in tumor tissue, Ab-IR700 is irradiated with 690 nm NIR light, which initiates a photochemical reaction that selectively damages the cell membrane of target cells, thereby inducing immunogenic cell death. Its high tumor selectivity and therapeutic efficacy establish NIR-PIT as a promising next-generation cancer therapy. However, its further application to deep-seated solid tumors remains challenging, and will require IR700 analogs and novel dye scaffolds that can be activated by longer-wavelength light to achieve greater tissue penetration and that offer greater photochemical activation efficiency. This review covers the activation mechanism of IR700, the mechanisms of cytotoxicity of NIR-PIT, emerging applications of NIR-PIT in oncology and infectious diseases, the range of dye delivery vehicles, and the development of new dyes for NIR-PIT.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":"1505-1519"},"PeriodicalIF":3.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13306961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346696","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}