ACS Chemical Biology最新文献

{"title":"Identification of a Selective Pharmacologic IRE1/XBP1s Activator with Enhanced Tissue Exposure.","authors":"Jie Sun, Kyunga Lee, Sergei Kutseikin, Adrian Guerrero, Bibiana Rius, Aparajita Madhavan, Chavin Buasakdi, Ka-Neng Cheong, Priyadarshini Chatterjee, Dorian A Rosen, Leonard Yoon, Maziar S Ardejani, Alejandra Mendoza, Jessica D Rosarda, Enrique Saez, Jeffery W Kelly, R Luke Wiseman","doi":"10.1021/acschembio.4c00867","DOIUrl":"10.1021/acschembio.4c00867","url":null,"abstract":"<p><p>Activation of the IRE1/XBP1s signaling arm of the unfolded protein response (UPR) has emerged as a promising strategy to mitigate etiologically diverse diseases. Despite this promise, few compounds are available to selectively activate IRE1/XBP1s signaling to probe the biologic and therapeutic implications of this pathway in human disease. Recently, we identified the compound IXA4 as a highly selective activator of protective IRE1/XBP1s signaling. While IXA4 has proven useful for increasing IRE1/XBP1s signaling in cultured cells and mouse liver, the utility of this compound is restricted by its limited activity in other tissues. To broaden our ability to pharmacologically interrogate the impact of IRE1/XBP1s signaling <i>in vivo</i>, we sought to identify IRE1/XBP1s activators with greater tissue activity than IXA4. We reanalyzed 'hits' from the high throughput screen used to identify IXA4, selecting compounds from structural classes not previously pursued. We then performed global RNAseq to confirm that these compounds showed transcriptome-wide selectivity for IRE1/XBP1s activation. Functional profiling revealed compound IXA62 as a selective IRE1/XBP1s activator that reduced Aβ secretion from CHO^7PA2 cells and enhanced glucose-stimulated insulin secretion from rat insulinoma cells, mimicking the effects of IXA4 in these assays. IXA62 robustly and selectively activated IRE1/XBP1s signaling in the liver of mice dosed compound intraperitoneally or orally. In treated mice, IXA62 showed broader tissue activity, relative to IXA4, inducing expression of IRE1/XBP1s target genes in additional tissues such as kidney and lung. Collectively, our results designate IXA62 as a selective IRE1/XBP1s signaling activating compound with enhanced tissue activity, which increases our ability to pharmacologically probe the biologic significance and potential therapeutic utility of enhancing adaptive IRE1/XBP1s signaling <i>in vivo</i>.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"993-1003"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotoxic Implications of Human Coronaviruses in Neurodegenerative Diseases: A Perspective from Amyloid Aggregation.","authors":"Thi Hong Van Nguyen, Francois Ferron, Kazuma Murakami","doi":"10.1021/acschembio.5c00153","DOIUrl":"10.1021/acschembio.5c00153","url":null,"abstract":"<p><p>Human coronaviruses (HCoVs) include seven species: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1, and SARS-CoV-2. The last three, classified as <i>Betacoronaviruses</i>, are highly transmissible and have caused severe pandemics. HCoV infections primarily affect the respiratory system, leading to symptoms such as dry cough, fever, and breath shortness, which can progress to acute respiratory failure and death. Beyond respiratory effects, increasing evidence links HCoVs to neurological dysfunction. However, distinguishing direct neural complications from preexisting disorders, particularly in the elderly, remains challenging. This study examines the association between HCoVs and neurodegenerative diseases like Alzheimer disease, Parkinson disease, Lewy body dementia, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. It also presents the long-term neurological effects of HCoV infections and their differential impact across age groups and sexes. A key aspect of this study is the investigation of the sequence and structural similarities between amyloidogenic and HCoV spike proteins, which can provide insights into potential neuropathomechanisms.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"983-992"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential of Homologous Recombination Protein PALB2 in Synthetic Lethal Combinations.","authors":"Xinyan Lu, Basilius Sauter, Aramis Keller, Saule Zhanybekova, Dennis Gillingham","doi":"10.1021/acschembio.5c00111","DOIUrl":"10.1021/acschembio.5c00111","url":null,"abstract":"<p><p>Cells with defective homologous recombination (HR) are highly sensitive to poly(ADP-ribose) polymerase (PARP) inhibition. Current therapeutic approaches leverage this vulnerability by using PARP inhibitors in cells with genetically compromised HR. However, if HR factors in cancer cells could be inhibited or degraded pharmacologically, it might reveal other opportunities for synergistic combinations. In this study, we developed a model system that recapitulates PARP/HR synthetic lethality by integrating a small-molecule responsive zinc-finger degron into the HR factor Partner and Localizer of BRCA2 (PALB2). We further tested a series of peptide ligands for PALB2 based on its natural binding partners, which led to the discovery of a high affinity peptide that will support future work on PALB2 and HR. Together, our findings validate PALB2 as a promising drug target and provide the tools and starting points for developing molecules with therapeutic applications.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"1099-1106"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and Characterization of Small Molecule Inhibitors Targeting Exonuclease 1 for Homologous Recombination-Deficient Cancer Therapy.","authors":"Yixing Wang, Jessica D Hess, Chen Wang, Lingzi Ma, Megan Luo, Jennifer Jossart, John J Perry, David Kwon, Zhe Wang, Xinyu Pei, Changxian Shen, Yingying Wang, Mian Zhou, Holly Yin, David Horne, André Nussenzweig, Li Zheng, Binghui Shen","doi":"10.1021/acschembio.5c00117","DOIUrl":"https://doi.org/10.1021/acschembio.5c00117","url":null,"abstract":"<p><p>Human exonuclease 1 (EXO1), a member of the structure-specific nuclease family, plays a critical role in maintaining genome stability by processing DNA double-strand breaks (DSBs), nicks, and replication intermediates during DNA replication and repair. As its exonuclease activity is essential for homologous recombination (HR) and replication fork processing, EXO1 has emerged as a compelling therapeutic target, especially in cancers marked by heightened DNA damage and replication stress. Through high-throughput screening of 45,000 compounds, we identified seven distinct chemical scaffolds that demonstrated effective and selective inhibition of EXO1. Representative compounds from two of the most potent scaffolds, C200 and F684, underwent a comprehensive docking analysis and subsequent site-directed mutagenesis studies to evaluate their binding mechanisms. Biochemical assays further validated their potent and selective inhibition of the EXO1 nuclease activity. Tumor cell profiling experiments revealed that these inhibitors exploit synthetic lethality in BRCA1-deficient cells, emphasizing their specificity and therapeutic potential for targeting genetically HR-deficient (HRD) cancers driven by deleterious mutations in HR genes like BRCA1/2. Mechanistically, EXO1 inhibition suppressed DNA end resection, stimulated the accumulation of DNA double-strand breaks, and triggered S-phase PARylation, effectively disrupting DNA repair pathways that are essential for cancer cell survival. These findings establish EXO1 inhibitors as promising candidates for the treatment of HRD cancers and lay the groundwork for the further optimization and development of these compounds as targeted therapeutics.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Escherichia coli</i> <i>yybP-ykoY</i> Riboswitch as a Tandem Riboswitch Regulated by Mn²⁺ and pH.","authors":"Wenwen Xiao, Guangfeng Liu, Ting Chen, Yunlong Zhang, Ailong Ke, Rujie Cai, Changrui Lu","doi":"10.1021/acschembio.4c00715","DOIUrl":"10.1021/acschembio.4c00715","url":null,"abstract":"<p><p>The <i>Escherichia</i><i>coli</i> <i>yybP-ykoY</i> riboswitch regulates <i>mntP</i> and <i>alx</i> gene expression on the translation level. It contains two tandem domains regulated by Mn²⁺ and pH. This study investigates the tertiary structure and conformational dynamics of the <i>E. coli</i> <i>yybP-ykoY</i> riboswitch using a combination of crystallography, small-angle X-ray scattering (SAXS), and chemical probing. Our crystal structure of the aptamer domain at 3.8 Å reveals that the <i>yybP-ykoY</i> riboswitch aptamer domain forms a coaxial superhelix containing three helices connected by a three-way junction (3WJ), with L1 and L3 creating a pocket-like structure that binds Mg²⁺ and Mn²⁺. SHAPE probing and SAXS show that the <i>yybP-ykoY</i> riboswitch maintains a consistent conformation across pH conditions without Mn²⁺ but exhibits significant conformational changes under alkaline conditions when Mn²⁺ is present. These findings align with our proposed model, where Mn²⁺ binding induces a transition from an \"OFF\" to an \"ON\" state in alkaline conditions, while the Mn²⁺ remains bound to the aptamer independent of pH. This regulatory mechanism allows for more sophisticated control of gene expression, providing a finely tuned adaptive response to environmental changes.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"1010-1019"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosynthesis of Physcion and Identification of an O-Methyltransferase with C6-OH Selectivity in <i>Aspergillus chevalieri</i> BYST01.","authors":"Zhong-di Huang, Shu-Xiang Zhang, Ye Wang, Zhi-Wen Song, Wei-Yu Wang, Cai-Ping Yin, Ying-Lao Zhang","doi":"10.1021/acschembio.5c00004","DOIUrl":"10.1021/acschembio.5c00004","url":null,"abstract":"<p><p>Physcion, a polyketide natural product derived from plants and microorganisms, has been commercially approved as an agricultural fungicide for the prevention and treatment of powdery mildew. However, the long planting period and complex extraction process from plants limit the yield of physcion. Here, the <i>Phy</i> biosynthetic gene cluster responsible for physcion biosynthesis was identified from the genome of high-yield physcion strain <i>Aspergillus chevalieri</i> BYST01. We reconstructed the biosynthesis of physcion via heterologous expression of <i>PhyFGL</i> in <i>Aspergillus oryzae</i> NSAR1. Of note, the PT domain of <i>PhyG</i> catalyzes the selective ring closure to form two distinct polyketide scaffolds (<b>1</b> and <b>7</b>) and for the first time to report the biosynthetic pathway of compound pannorin C (<b>1</b>). In addition, in vitro and in vivo enzymatic assays demonstrated that PhyL had the capability to catalyze the stereoselective methylation of C6-OH. The physiological biosynthetic pathway was further rationally engineered by improving the catalytic efficiency of O-methyltransferase (OMT)-PhyL by 2.64-fold through site-directed mutagenesis. Subsequently, the titer of physcion reached 152.81 mg/L in shake-flask fermentation through optimizing the cultivation conditions and alkaline treatment of the fermentation broth. Furthermore, the novel CYP-PhyE could with regioselectivity catalyze symmetrically oxidative phenol coupling (OPC) of monomeric polyketone to form 10,10'-dimers. Finally, differential expression analysis of transcriptome between <i>AO-PhyGF</i> and <i>AO-PhyGFL</i> revealed that the expression of the <i>PhyL</i> gene led to extensive alterations in the secondary metabolism of <i>A. oryzae</i> NSAR1 and upregulating the expression level of ABC transporters, promoting the translocation of host metabolites. Thus, our study provides a foundation for further improving the production of physcion via a highly efficient route.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"1048-1058"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the Role of the Competence Regulon Quorum Sensing Circuitry in <i>Streptococcus cristatus</i>.","authors":"Alec A Brennan, Steven C Tata, Clay P Renshaw, Yftah Tal-Gan","doi":"10.1021/acschembio.5c00180","DOIUrl":"10.1021/acschembio.5c00180","url":null,"abstract":"<p><p><i>Streptococcus cristatus</i> belongs to the Mitis group of streptococci and is an early colonizer of the human oral cavity. This species has recently been reclassified from <i>Streptococcus oligofermentans</i>, and as such, much information regarding the competence regulon and its regulatory role in modulating downstream phenotypes remains unknown. In this work, we set out to investigate the role of the competence-stimulating peptide (CSP) in competence regulon activation and modulation, as well as define the resultant transcriptomic and phenotypic effects of CSP exposure. To this end, following confirmation of the CSP identity, structure activity relationship (SAR) analyses were conducted and revealed residues integral for CSP::ComD binding and activation, as well as provided insights about the CSP secondary structure. The ability of synthesized CSP analogs to modulate the competence regulon was quantified with the aid of a newly developed luciferase-based reporter strain, after which the biological activity was correlated with peptide secondary structure derived through CD analysis. Furthermore, RNA-seq was utilized to gain broader insights about subsequent transcriptomic changes following CSP incubation, while phenotypic assays helped with visualizing resultant expression profiles. Lastly, to further explore the potential of <i>S. cristatus</i> as a potential biotherapeutic against the oral pathogen, <i>Streptococcus mutans</i>, interspecies competition assays were used to evaluate interactions between these two species.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"1123-1136"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual SLIPT-A Lipid Mimic to Enable Spatiotemporally Defined, Sequential Protein Dimerization.","authors":"Kristina V Bayer, Maedeh Taeb, Birgit Koch, Shige H Yoshimura, Richard Wombacher","doi":"10.1021/acschembio.4c00856","DOIUrl":"10.1021/acschembio.4c00856","url":null,"abstract":"<p><p>Spatiotemporal control of proteins is crucial for cellular phenomena such as signal integration, propagation, as well as managing crosstalk. In membrane-associated signaling, this regulation is often enabled by lipids, wherein highly dynamic, sequential recruitment of interacting proteins is key to successful signaling. Here, we present dual SLIPT (self-localizing ligand-induced protein translocation), a lipid-analog tool, capable of emulating this lipid-mediated sequential recruitment of any two proteins of interest. Dual SLIPT self-localizes to the inner leaflet of the plasma membrane (PM). There, dual SLIPT presents trimethoprim (TMP) and HaloTag ligand (HTL) to cytosolic proteins of interest (POIs), whereupon POIs fused to the protein tags ^iK6eDHFR, or to HOB are recruited. A systematic extension of the linkers connecting the two mutually orthogonal headgroups was implemented to overcome the steric clash between the recruited POIs. Using Förster resonance energy transfer (FRET), we verify that the resulting probe is capable of simultaneous binding of both proteins of interest, as well as their dimerization. Dual SLIPT was found to be particularly suitable for use in physiologically relevant concentrations, such as recruitment via tightly regulated, transient lipid species. We further expanded dual SLIPT to the photocontrollable dual SLIPT^NVOC, by introducing a photocaging group onto the TMP moiety. Dual SLIPT^NVOC enables sequential and spatiotemporally defined dimerization upon blue light irradiation. Thus, dual SLIPT^NVOC serves as a close mimic of physiology, enabling interrogation of dynamic cytosol-to-plasma membrane recruitment events and their impact on signaling.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"1038-1047"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical Characterization of Disease-Associated Variants of Human Ornithine Transcarbamylase.","authors":"Emily Micheloni, Samantha S Watson, Penny J Beuning, Mary Jo Ondrechen","doi":"10.1021/acschembio.5c00043","DOIUrl":"10.1021/acschembio.5c00043","url":null,"abstract":"<p><p>Human ornithine transcarbamylase deficiency (OTCD) is the most common ureagenesis disorder in the world. OTCD is an X-linked genetic deficiency in which patients experience hyperammonemia to varying degrees depending on the severity of the genetic mutation. More than two-thirds of the known mutations are caused by single nucleotide substitutions. In this paper, partial order optimum likelihood (POOL), a machine learning method, is used to analyze single nucleotide substitutions in OTC with varying disease phenotypes and predicted catalytic efficiencies. Specifically, we used a computed metric, μ₄, a measure of the degree of coupling between an ionizable residue and its neighbors, calculated for the catalytic residues, to identify which protein variants were most likely to have impacted catalytic activities. From this analysis, 17 disease-associated variants were selected plus one additional variant, representing a range of μ₄ values and POOL ranks. Then μ₄ predictions were compared with established bioinformatics tools, SIFT, PolyPhen-2, Provean, FATHMM, MutPred2, and MutationTaster2. The bioinformatics tools predicted that most of these mutations are deleterious. The variants were biochemically characterized using kinetics assays, size exclusion chromatography, and differential scanning fluorimetry. POOL combined with μ₄ analysis was able to predict correctly which variants were catalytically hindered in vitro for 17 out of 18 variants. Then by expressing a subset of these proteins in cell culture, mechanisms for disease were proposed. Analysis using μ₄ is a complementary method to the sequence-based bioinformatics tools for predicting the effects of mutation on catalytic function.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"1059-1067"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Insights into Spare-Tire DNA G-Quadruplex from the Human <i>VEGF</i> Promoter.","authors":"Ines Burkhart, Vivien Rose McKenney, Julia Wirmer-Bartoschek, J Tassilo Grün, Alexander Heckel, Harald Schwalbe","doi":"10.1021/acschembio.5c00226","DOIUrl":"https://doi.org/10.1021/acschembio.5c00226","url":null,"abstract":"<p><p>The vascular endothelial growth factor (<i>VEGF</i>) promoter region, which is involved in cancer progression, contains guanine-rich sequences capable of forming G-quadruplex (G4) structures. G4s play a critical role in transcriptional regulation and genomic stability and exhibit high structural polymorphism. The major <i>VEGF</i> G4 adopts a parallel topology involving the first four of five G-tracts (<i>VEGF</i>1234), while a potential \"spare-tire\" mechanism suggests the formation of <i>VEGF</i>1245 in response to oxidative damage. Here, we characterize this alternative G4 (<i>VEGF</i>1245), formed by excluding the third G-tract, using circular dichroism and nuclear magnetic resonance spectroscopy. Structural analysis reveals that <i>VEGF</i>1245 folds in a hybrid conformation. Different from the other five tracts containing G4s, for which various strand topologies can rapidly interconvert, <i>VEGF</i>1245 remains thermodynamically metastable and does not refold spontaneously into <i>VEGF</i>1234 at physiological temperatures. Further trapping of the <i>VEGF</i>1245 conformation by a photolabile protecting group and its in situ release documents that the transition to <i>VEGF</i>1234 requires elevated temperatures, implicating kinetic barriers in the refolding process and the delineation of <i>VEGF</i>1245 as a prominent metastable conformation. Our findings provide new insights into transcriptional regulation and DNA repair for cancer-related <i>VEGF</i>-G4.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}