ACS Central Science最新文献

{"title":"Metalplant Farms Chemicals for the Clean Energy Transition","authors":"Diana Kruzman,&nbsp;","doi":"10.1021/acscentsci.5c0004910.1021/acscentsci.5c00049","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00049https://doi.org/10.1021/acscentsci.5c00049","url":null,"abstract":"<p >The phytomining start-up is using plants to extract nickel from Albania’s soil.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"170–172 170–172"},"PeriodicalIF":12.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single Dose of a Small Molecule Leads to Complete Regressions of Large Breast Tumors in Mice","authors":"Michael P. Mulligan,&nbsp;Matthew W. Boudreau,&nbsp;Brooke A. Bouwens,&nbsp;Yoongyeong Lee,&nbsp;Hunter W. Carrell,&nbsp;Junyao Zhu,&nbsp;Spyro Mousses,&nbsp;David J. Shapiro,&nbsp;Erik R. Nelson,&nbsp;Timothy M. Fan and Paul J. Hergenrother*,&nbsp;","doi":"10.1021/acscentsci.4c0162810.1021/acscentsci.4c01628","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01628https://doi.org/10.1021/acscentsci.4c01628","url":null,"abstract":"<p >Patients with estrogen receptor α positive (ERα+) breast cancer typically undergo surgical resection, followed by 5–10 years of treatment with adjuvant endocrine therapy. This prolonged intervention is associated with a host of undesired side effects that reduce patient compliance, and ultimately therapeutic resistance and disease relapse/progression are common. An ideal anticancer therapy would be effective against recurrent and refractory disease with minimal dosing; however, there is little precedent for marked tumor regression with a single dose of a small molecule therapeutic. Herein we report <b>ErSO-TFPy</b> as a small molecule that induces quantitative or near-quantitative regression of tumors in multiple mouse models of breast cancer with a single dose. Importantly, this effect is robust and independent of tumor size with eradication of even very large tumors (500−1500 mm³) observed. Mechanistically, these tumor regressions are a consequence of rapid induction of necrotic cell death in the tumor and are immune cell independent. If successfully translated to human cancer patients, the benefits of such an anticancer drug that is effective with a single dose would be significant.</p><p >A single dose of <b>ErSO-TFPy</b> leads to complete tumor regressions in multiple mouse xenograft models of breast cancer.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"228–238 228–238"},"PeriodicalIF":12.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01628","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-Functional Antibiotic Adjuvant Displays Potency against Complicated Gram-Negative Bacterial Infections and Exhibits Immunomodulatory Properties","authors":"Geetika Dhanda,&nbsp;Himani Singh,&nbsp;Abhinav Gupta,&nbsp;Sk Abdul Mohid,&nbsp;Karishma Biswas,&nbsp;Riya Mukherjee,&nbsp;Smriti Mukherjee,&nbsp;Anirban Bhunia,&nbsp;Nisanth N. Nair and Jayanta Haldar*,&nbsp;","doi":"10.1021/acscentsci.4c0206010.1021/acscentsci.4c02060","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02060https://doi.org/10.1021/acscentsci.4c02060","url":null,"abstract":"<p >The treatment of Gram-negative bacterial infections is challenged by antibiotic resistance and complicated forms of infection like persistence, multispecies biofilms, intracellular infection, as well as infection-associated hyperinflammation and sepsis. To overcome these challenges, a dual-functional antibiotic adjuvant has been developed as a novel strategy to target complicated forms of bacterial infection and exhibit immunomodulatory properties. The lead adjuvant, D-LBDiphe showed multimodal mechanisms of action like weak outer membrane permeabilization, weak membrane depolarization, and inhibition of efflux machinery, guided primarily by hydrogen bonding and electrostatic interactions, along with weak van der Waals forces. D-LBDiphe potentiated antibiotics up to ∼4100-fold, targeted phenotypic forms of antibiotic tolerance, and revitalized antibiotics against topical and systemic infections of <i>P. aeruginosa</i> in mice. The aromatic moiety in D-LBDiphe was instrumental for interaction with lipopolysaccharide (LPS) micelles, and this interaction was the driving factor in reducing pro-inflammatory cytokines by 61.8–79% in mice challenged with LPS. Such multifarious properties of a weak-membrane perturbing, nonactive and nontoxic adjuvant have been discussed for the first time, supported by detailed mechanistic understanding and elucidation of structure-guided properties. This work expands the scope of antibiotic adjuvants and validates them as a promising approach for treatment of complicated bacterial infections and inflammation.</p><p >D-LBDiphe is a dual-functional antibiotic adjuvant which potentiates antibiotics against complicated Gram-negative bacterial infections and reduces bacterial lipopolysaccharide induced inflammation.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"279–293 279–293"},"PeriodicalIF":12.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of Multiplexed Assays on Single Anisotropic Particles Using Microfluidics","authors":"Zengnan Wu,&nbsp;Yajing Zheng,&nbsp;Ling Lin*,&nbsp;Gaowa Xing,&nbsp;Tianze Xie,&nbsp;Jiaxu Lin,&nbsp;Xiaorui Wang and Jin-Ming Lin*,&nbsp;","doi":"10.1021/acscentsci.4c0200910.1021/acscentsci.4c02009","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02009https://doi.org/10.1021/acscentsci.4c02009","url":null,"abstract":"<p >Considerable efforts have been made to develop microscale multiplexing strategies. However, challenges remain due to the difficulty in deploying functional objects and decoding high-density signals on anisotropic microcarriers. Here, we report a microfluidic method to fabricate architecture-marked anisotropic particles for performing designable multiplexed assays in a label-free manner. By controlling fluid assembly and rapid in-air cross-linking, the particles are endowed with multiple functional regions and a unique architecture identifier. The marked architecture enables an addressing mechanism that allows the profiling of embedded label-free objects by mapping a well-defined reference architecture onto the target particle. By loading analytes of interest, such as molecular probes or cells, we showed the potential of these structurally flexible particles for detecting microRNAs and studying cell interactions. The architecture-marked particles represent a new approach for single-entity assays and can be the basis for exploring more advanced microscale multiplexed applications.</p><p >A microfluidic method is reported for creating architecture-marked hydrogel particles that enable encapsulation and analysis of label-free objects, advancing single-entity multiplexed assays.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"294–301 294–301"},"PeriodicalIF":12.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Europe Running out of Chemistry Teachers?","authors":"Vanessa Zainzinger,&nbsp;","doi":"10.1021/acscentsci.5c0003810.1021/acscentsci.5c00038","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00038https://doi.org/10.1021/acscentsci.5c00038","url":null,"abstract":"<p >As shortages of qualified teachers plague schools, the chemical sciences community worries about who will inspire the next generation of scientists.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"173–176 173–176"},"PeriodicalIF":12.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring the Elusive Half-Life of Samarium-146.","authors":"Mara Johnson-Groh","doi":"10.1021/acscentsci.4c02221","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02221","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 1","pages":"8-11"},"PeriodicalIF":12.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring the Elusive Half-Life of Samarium-146","authors":"Mara Johnson-Groh,&nbsp;","doi":"10.1021/acscentsci.4c0222110.1021/acscentsci.4c02221","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02221https://doi.org/10.1021/acscentsci.4c02221","url":null,"abstract":"<p >The isotope is critical for understanding Earth’s origins. Attempts at measuring its half-life have been plagued by errors, but a new approach offers hope.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 1","pages":"8–11 8–11"},"PeriodicalIF":12.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143088061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strand-Swapped SH3 Domain Dimer with Superoxide Dismutase Activity","authors":"Florian R. Häge,&nbsp;Merlin Schwan,&nbsp;Marcos Rafael Conde González,&nbsp;Jonas Huber,&nbsp;Stefan Germer,&nbsp;Matilde Macrì,&nbsp;Jürgen Kopp,&nbsp;Irmgard Sinning* and Franziska Thomas*,&nbsp;","doi":"10.1021/acscentsci.4c0134710.1021/acscentsci.4c01347","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01347https://doi.org/10.1021/acscentsci.4c01347","url":null,"abstract":"<p >The design of metalloproteins allows us to better understand metal complexation in proteins and the resulting function. In this study, we incorporated a Cu²⁺-binding site into a natural protein domain, the 58 amino acid c-Crk-SH3, to create a miniaturized superoxide dismutase model, termed SO1. The resulting low complexity metalloprotein was characterized for structure and function by circular dichroism and UV spectroscopy as well as EPR spectroscopy and X-ray crystallography. The miniprotein was found to be a strand-swapped dimer with an unusual coupled binuclear Type 2-like copper center in each protomer. SO1-Cu was found to be SOD-active with an activity only 1 order of magnitude lower than that of natural SOD enzymes and 1 to 2 orders of magnitude higher than that of other low-complexity SOD protein models of similar size. This serendipitous design provides us with a new structural template for future designs of binuclear metalloproteins with different metal ions and functions.</p><p >The catalytic copper site of human Cu,Zn Superoxide Dismutase 1 was grafted onto the c-Crk SH3 domain, resulting in a strand-swapped SH3 domain dimer with remarkable superoxide dismutase activity.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 1","pages":"157–166 157–166"},"PeriodicalIF":12.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143087861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strand-Swapped SH3 Domain Dimer with Superoxide Dismutase Activity.","authors":"Florian R Häge, Merlin Schwan, Marcos Rafael Conde González, Jonas Huber, Stefan Germer, Matilde Macrì, Jürgen Kopp, Irmgard Sinning, Franziska Thomas","doi":"10.1021/acscentsci.4c01347","DOIUrl":"10.1021/acscentsci.4c01347","url":null,"abstract":"<p><p>The design of metalloproteins allows us to better understand metal complexation in proteins and the resulting function. In this study, we incorporated a Cu²⁺-binding site into a natural protein domain, the 58 amino acid c-Crk-SH3, to create a miniaturized superoxide dismutase model, termed SO1. The resulting low complexity metalloprotein was characterized for structure and function by circular dichroism and UV spectroscopy as well as EPR spectroscopy and X-ray crystallography. The miniprotein was found to be a strand-swapped dimer with an unusual coupled binuclear Type 2-like copper center in each protomer. SO1-Cu was found to be SOD-active with an activity only 1 order of magnitude lower than that of natural SOD enzymes and 1 to 2 orders of magnitude higher than that of other low-complexity SOD protein models of similar size. This serendipitous design provides us with a new structural template for future designs of binuclear metalloproteins with different metal ions and functions.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 1","pages":"157-166"},"PeriodicalIF":12.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a Privileged Scaffold for Inhibition of Sterol Transport Proteins through the Synthesis and Ring Distortion of Diverse, Pseudo-Natural Products.","authors":"Frederik Simonsen Bro, Laura Depta, Nienke J Dekker, Hogan P Bryce-Rogers, Maria Lillevang Madsen, Kaia Fiil Præstegaard, Tino Petersson, Thomas Whitmarsh-Everiss, Mariusz Kubus, Luca Laraia","doi":"10.1021/acscentsci.4c01657","DOIUrl":"10.1021/acscentsci.4c01657","url":null,"abstract":"<p><p>Sterol transport proteins mediate intracellular sterol transport, organelle contact sites, and lipid metabolism. Despite their importance, the similarities in their sterol-binding domains have made the identification of selective modulators difficult. Herein we report a combination of different compound library synthesis strategies to prepare a cholic acid-inspired compound collection for the identification of potent and selective inhibitors of sterol transport proteins. The fusion of a primary sterol scaffold with a range of different fragments found in natural products followed by various ring distortions allowed the synthesis of diverse sterol-inspired compounds. This led to the identification of a complex and three-dimensional spirooxepinoindole as a privileged scaffold for sterol transport proteins. With careful optimization of the scaffold, the selectivity could be directed toward a single transporter, as showcased by the development of a potent and selective Aster-A inhibitor. We suggest that the combination of different design strategies is generally applicable for the identification of potent and selective bioactive compounds with drug-like properties.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 1","pages":"136-146"},"PeriodicalIF":12.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}