Cell Chemical Biology最新文献

Macrophages make “sense” of obesity-driven acidity in the TME

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.11.008

Spenser H. Stone, Jeffrey C. Rathmell, Jackie E. Bader

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FAAHcilitating recovery in malnourished kids

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.11.007

Franciscus Chandra, Elaine Y. Hsiao

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D-aring to explore: New approaches to gasdermin D targeting

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.11.006

Lei Wang, Wen Zhou

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Biogenesis and roles of tRNA queuosine modification and its glycosylated derivatives in human health and diseases

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-09 DOI: 10.1016/j.chembiol.2024.11.004

Tsutomu Suzuki, Atsuya Ogizawa, Kensuke Ishiguro, Asuteka Nagao

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Insights into biofilm architecture and maturation enable improved clinical strategies for exopolysaccharide-targeting therapeutics

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-04 DOI: 10.1016/j.chembiol.2024.11.005

J. Sebastian Temme, Zibin Tan, Mi Li, Mo Yang, Alexander Wlodawer, Xuefei Huang, John S. Schneekloth, Jeffrey C. Gildersleeve

{"title":"Insights into biofilm architecture and maturation enable improved clinical strategies for exopolysaccharide-targeting therapeutics","authors":"J. Sebastian Temme, Zibin Tan, Mi Li, Mo Yang, Alexander Wlodawer, Xuefei Huang, John S. Schneekloth, Jeffrey C. Gildersleeve","doi":"10.1016/j.chembiol.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.11.005","url":null,"abstract":"Polysaccharide intercellular adhesin (PIA), an exopolysaccharide composed of poly-N-acetyl glucosamine (PNAG), is an essential component in many pathogenic biofilms. Partial deacetylation of PNAG is required for biofilm formation, but limited structural knowledge hinders therapeutic development. Employing a new monoclonal antibody (TG10) that selectively binds highly deacetylated PNAG and an antibody (F598) in clinical trials that binds highly acetylated PNAG, we demonstrate that PIA within the biofilm contains distinct regions of highly acetylated and deacetylated exopolysaccharide, contrary to the previous model invoking stochastic deacetylation throughout the biofilm. This discovery led us to hypothesize that targeting both forms of PNAG would enhance efficacy. Remarkably, TG10 and F598 synergistically increased in vitro and in vivo activity, providing 90% survival in a lethal Staphylococcus aureus challenge murine model. Our advanced model deepens the conceptual understanding of PIA architecture and maturation and reveals improved design strategies for PIA-targeting therapeutics, vaccines, and diagnostic agents.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"9 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Platelets accelerate lipid peroxidation and induce pathogenic neutrophil extracellular trap release

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-03 DOI: 10.1016/j.chembiol.2024.11.003

Madoka Ono, Masayasu Toyomoto, Momono Yamauchi, Masatoshi Hagiwara

{"title":"Platelets accelerate lipid peroxidation and induce pathogenic neutrophil extracellular trap release","authors":"Madoka Ono, Masayasu Toyomoto, Momono Yamauchi, Masatoshi Hagiwara","doi":"10.1016/j.chembiol.2024.11.003","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.11.003","url":null,"abstract":"Neutrophil extracellular traps (NETs), an important host defense mechanism, are assembled after the release of decondensed chromatin and other nuclear components by a process termed NETosis. However, excessive NET release destroys surrounding tissues, leading to conditions such as sepsis where platelets are implicated in the pathogenic switch of NETosis. Here, we show that platelets trigger iron accumulation and promote lipid peroxide production in neutrophils co-stimulated with lipopolysaccharide and platelets in vitro, resulting in the induction of NETosis. We also screened for compounds that inhibit lipid peroxidation, identified 8-methyl-N-geranyl-6-nonamide (capsaicin), and assessed its potential in suppressing platelet-mediated pathogenic NETosis. Capsaicin inhibited lipopolysaccharide/platelet-induced cellular lipid peroxidation and suppressed NETosis in vitro. Furthermore, capsaicin attenuated NETosis in a mouse model of lipopolysaccharide-induced lung inflammation. Our findings provide an original therapeutic strategy to target lipid peroxidation and pave the way for drug development for a wide range of NETosis-related diseases.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"13 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-02 DOI: 10.1016/j.chembiol.2024.11.001

引用次数: 0

An engineered cereblon optimized for high throughput screening and molecular glue discovery 为高通量筛选和分子胶发现而优化的工程脑龙

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-11-27 DOI: 10.1016/j.chembiol.2024.11.002

Henry J. Bailey, Jonathan Eisert, Rubina Kazi, Jan Gerhartz, Dominika Ewa Pieńkowska, Ina Dressel, Joshua Vollrath, Ivan Kondratov, Tetiana Matviyuk, Nataliya Tolmachova, Varun Jayeshkumar Shah, Giulio Giuliani, Thorsten Mosler, Thomas M. Geiger, Ana M. Esteves, Sandra P. Santos, Raquel L. Sousa, Tiago M. Bandeiras, Eva-Maria Leibrock, Ulrike Bauer, Ivan Dikic

{"title":"An engineered cereblon optimized for high throughput screening and molecular glue discovery","authors":"Henry J. Bailey, Jonathan Eisert, Rubina Kazi, Jan Gerhartz, Dominika Ewa Pieńkowska, Ina Dressel, Joshua Vollrath, Ivan Kondratov, Tetiana Matviyuk, Nataliya Tolmachova, Varun Jayeshkumar Shah, Giulio Giuliani, Thorsten Mosler, Thomas M. Geiger, Ana M. Esteves, Sandra P. Santos, Raquel L. Sousa, Tiago M. Bandeiras, Eva-Maria Leibrock, Ulrike Bauer, Ivan Dikic","doi":"10.1016/j.chembiol.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.11.002","url":null,"abstract":"The majority of clinical degraders utilize an immunomodulatory imide drug (IMiD)-based derivative that directs their target to the E3 ligase receptor cereblon (CRBN); however, identification of IMiD molecular glue substrates has remained underexplored. To tackle this, we design human CRBN constructs, which retain all features for ternary complex formation, while allowing generation of homogenous and cost-efficient expression in E. coli. Extensive profiling of the construct shows it to be the “best of both worlds” in terms of binding activity and ease of production. We next designed the “Enamine focused IMiD library” and demonstrated applicability of the construct to high-throughput screening, identifying binders with high potency, ligand efficiency, and specificity. Finally, we adapt our construct for proof of principle glue screening approaches enabling IMiD cellular interactome determination. Coupled with our IMiD binding landscape the methods described here should serve as valuable tools to assist discovery of next generation CRBN glues.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"113 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic induction of ferroptosis in tumors using PD-L1 targeting antibody nanogel conjugates 利用 PD-L1 靶向抗体纳米凝胶共轭物治疗诱导肿瘤中的铁变态反应

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-11-26 DOI: 10.1016/j.chembiol.2024.10.014

Mengdie Wang, Theeraphop Prachyathipsakul, Christi A. Wisniewski, Choua Xiong, Shivam Goel, Hira Lal Goel, Emmet R. Karner, Dimpi Mukhopadhyay, Prachi Gupta, Aniket Majee, S. Thayumanavan, Arthur M. Mercurio

{"title":"Therapeutic induction of ferroptosis in tumors using PD-L1 targeting antibody nanogel conjugates","authors":"Mengdie Wang, Theeraphop Prachyathipsakul, Christi A. Wisniewski, Choua Xiong, Shivam Goel, Hira Lal Goel, Emmet R. Karner, Dimpi Mukhopadhyay, Prachi Gupta, Aniket Majee, S. Thayumanavan, Arthur M. Mercurio","doi":"10.1016/j.chembiol.2024.10.014","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.10.014","url":null,"abstract":"Although programmed cell death ligand 1 (PD-L1) is best known for its role in immune suppression, tumor-intrinsic functions are emerging. Here, we report that tumor cells that express PD-L1 are sensitive to ferroptosis inducers such as imidazole ketone erastin (IKE). PD-L1 promotes ferroptosis sensitivity because it suppresses SLC7A11 expression and diminishes glutathione levels. Although the use of anti-PD-L1 antibody drug conjugates (ADCs) could be effective for the delivery of ferroptosis inducers to specific tumor populations, the chemistry of most ferroptosis inducers precludes their incorporation in ADCs. To overcome this challenge, we synthesized an antibody nanogel conjugate (ANC) comprised of an anti-PD-L1 antibody conjugated to a nanogel encapsulated with IKE. This ANC targets PD-L1-expressing cells in vitro and in vivo and induces ferroptosis, resulting in tumor suppression. Importantly, this approach is superior to systemic administration of IKE because it enables enhanced delivery of IKE specifically to tumor cells and it requires lower drug doses for efficacy.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"65 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Covalent targeting of splicing in T cells T 细胞剪接的共价靶向作用

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-11-25 DOI: 10.1016/j.chembiol.2024.10.010

Kevin A. Scott, Hiroyuki Kojima, Nathalie Ropek, Charles D. Warren, Tiffany L. Zhang, Simon J. Hogg, Henry Sanford, Caroline Webster, Xiaoyu Zhang, Jahan Rahman, Bruno Melillo, Benjamin F. Cravatt, Jiankun Lyu, Omar Abdel-Wahab, Ekaterina V. Vinogradova

{"title":"Covalent targeting of splicing in T cells","authors":"Kevin A. Scott, Hiroyuki Kojima, Nathalie Ropek, Charles D. Warren, Tiffany L. Zhang, Simon J. Hogg, Henry Sanford, Caroline Webster, Xiaoyu Zhang, Jahan Rahman, Bruno Melillo, Benjamin F. Cravatt, Jiankun Lyu, Omar Abdel-Wahab, Ekaterina V. Vinogradova","doi":"10.1016/j.chembiol.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.10.010","url":null,"abstract":"Despite significant interest in therapeutic targeting of splicing, few chemical probes are available for the proteins involved in splicing. Here, we show that elaborated stereoisomeric acrylamide EV96 and its analogues lead to a selective T cell state-dependent loss of interleukin 2-inducible T cell kinase (ITK) by targeting one of the core splicing factors SF3B1. Mechanistic investigations suggest that the state-dependency stems from a combination of differential protein turnover rates and extensive ITK mRNA alternative splicing. We further introduce the most comprehensive list to date of proteins involved in splicing and leverage cysteine- and protein-directed activity-based protein profiling with electrophilic scout fragments to demonstrate covalent ligandability for many classes of splicing factors and splicing regulators in T cells. Taken together, our findings show how chemical perturbation of splicing can lead to immune state-dependent changes in protein expression and provide evidence for the broad potential to target splicing factors with covalent chemistry.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"1 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0