ACS Central Science最新文献

Measuring the Elusive Half-Life of Samarium-146.

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-01-13 eCollection Date: 2025-01-22 DOI: 10.1021/acscentsci.4c02221

Mara Johnson-Groh

引用次数: 0

Strand-Swapped SH3 Domain Dimer with Superoxide Dismutase Activity.

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-01-10 eCollection Date: 2025-01-22 DOI: 10.1021/acscentsci.4c01347

Florian R Häge, Merlin Schwan, Marcos Rafael Conde González, Jonas Huber, Stefan Germer, Matilde Macrì, Jürgen Kopp, Irmgard Sinning, Franziska Thomas

{"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":"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.","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}

引用次数: 0

Identification of a Privileged Scaffold for Inhibition of Sterol Transport Proteins through the Synthesis and Ring Distortion of Diverse, Pseudo-Natural Products.

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-01-09 eCollection Date: 2025-01-22 DOI: 10.1021/acscentsci.4c01657

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

{"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":"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.","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}

引用次数: 0

Selection of Early Life Codons by Ultraviolet Light.

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-01-08 eCollection Date: 2025-01-22 DOI: 10.1021/acscentsci.4c01623

Corinna L Kufner, Stefan Krebs, Marlis Fischaleck, Julia Philippou-Massier, Helmut Blum, Dominik B Bucher, Dieter Braun, Wolfgang Zinth, Christof B Mast

{"title":"Selection of Early Life Codons by Ultraviolet Light.","authors":"Corinna L Kufner, Stefan Krebs, Marlis Fischaleck, Julia Philippou-Massier, Helmut Blum, Dominik B Bucher, Dieter Braun, Wolfgang Zinth, Christof B Mast","doi":"10.1021/acscentsci.4c01623","DOIUrl":"10.1021/acscentsci.4c01623","url":null,"abstract":"How life developed in its earliest stages is a central but notoriously difficult question in science. The earliest lifeforms likely used a reduced set of codon sequences that were progressively completed over time, driven by chemical, physical, and combinatorial constraints. However, despite its importance for prebiotic chemistry, UV radiation has not been considered a selection pressure for the evolution of early codon sequences. In this proof-of-principle study, we quantified the UV susceptibility of large pools of DNA protogenomes and tested the timing of evolutionary incorporation of codon sequences using a Monte Carlo method utilizing sequence-context-dependent damage rates previously determined by high throughput sequencing experiments. We traced the UV-radiation selection pressure on early protogenomes comprising a limited number of codon sequences to late protogenomes with access to all codons. The modeling showed that in just minutes under early sunlight, the choice of the first codons determined whether most of the protogenomes remained intact or became damaged entirely. The results correlated with earlier chemical models of the evolution of the genetic code. Our results show how UV could have played a crucial role in the evolution of the early genetic code for a DNA-based genome and provide the concept for future RNA-based studies.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 1","pages":"147-156"},"PeriodicalIF":12.7,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044858","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}

引用次数: 0

Wash-free Imaging in Live Cells. 活细胞免洗成像

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-01-06 eCollection Date: 2025-01-22 DOI: 10.1021/acscentsci.4c02083

Mahdi Hasan, Ashraf Brik

引用次数: 0

NSF NeXUS: A New Model for Accessing the Frontiers of Ultrafast Science.

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-01-06 eCollection Date: 2025-01-22 DOI: 10.1021/acscentsci.4c01682

L Robert Baker, Louis F DiMauro, Claudia Turro, Jay A Gupta, Roland K Kawakami, Thomas K Allison, Theodore J Ronningen, Timothy D Scarborough, Vyacheslav Leshchenko, Seth S Shields, John E Beetar

引用次数: 0

Identifying Opportunity Targets in Gram-Negative Pathogens for Infectious Disease Mitigation. 识别革兰氏阴性病原体中的机会目标，缓解传染病。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-01-03 eCollection Date: 2025-01-22 DOI: 10.1021/acscentsci.4c01437

Isaac A Paddy, Laura M K Dassama

{"title":"Identifying Opportunity Targets in Gram-Negative Pathogens for Infectious Disease Mitigation.","authors":"Isaac A Paddy, Laura M K Dassama","doi":"10.1021/acscentsci.4c01437","DOIUrl":"10.1021/acscentsci.4c01437","url":null,"abstract":"Antimicrobial drug resistance (AMR) is a pressing global human health challenge. Humans face one of their grandest challenges as climate change expands the habitat of vectors that bear human pathogens, incidences of nosocomial infections rise, and new antibiotics discovery lags. AMR is a multifaceted problem that requires a multidisciplinary and an \"all-hands-on-deck\" approach. As chemical microbiologists, we are well positioned to understand the complexities of AMR while seeing opportunities for tackling the challenge. In this Outlook, we focus on vulnerabilities of human pathogens and posit that they represent \"opportunity targets\" for which few modulatory ligands exist. We center our attention on proteins in Gram-negative organisms, which are recalcitrant to many antibiotics because of their external membrane barrier. Our hope is to highlight such targets and explore their potential as \"druggable\" proteins for infectious disease mitigation. We posit that success in this endeavor will introduce new classes of antibiotics that might alleviate some of the current pressing AMR concerns.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 1","pages":"25-35"},"PeriodicalIF":12.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044846","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}

引用次数: 0

Enhancing the Optically Detected Magnetic Resonance Signal of Organic Molecular Qubits.

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-01-03 eCollection Date: 2025-01-22 DOI: 10.1021/acscentsci.4c01632

Yong Rui Poh, Joel Yuen-Zhou

{"title":"Enhancing the Optically Detected Magnetic Resonance Signal of Organic Molecular Qubits.","authors":"Yong Rui Poh, Joel Yuen-Zhou","doi":"10.1021/acscentsci.4c01632","DOIUrl":"10.1021/acscentsci.4c01632","url":null,"abstract":"In quantum information science and sensing, electron spins are often purified into a specific polarization through an optical-spin interface, a process known as optically detected magnetic resonance (ODMR). Diamond-NV centers and transition metals are both excellent platforms for these so-called color centers, while metal-free molecular analogues are also gaining popularity for their extended polarization lifetimes, milder environmental impacts, and reduced costs. In our earlier attempt at designing such organic high-spin π-diradicals, we proposed to spin-polarize by shelving triplet M S = ±1 populations as singlets. This was recently verified by experiments albeit with low ODMR contrasts of <1% at temperatures above 5 K. In this work, we propose to improve the ODMR signal by moving singlet populations back into the triplet M S = 0 sublevel, designing a true carbon-based molecular analogue to the NV center. Our proposal is based upon transition-orbital and group-theoretical analyses of beyond-nearest-neighbor spin-orbit couplings, which are further confirmed by ab initio calculations of a realistic trityl-based radical dimer. Microkinetic analyses point toward high ODMR contrasts of around 30% under experimentally feasible conditions, a stark improvement from previous works. Finally, in our quest toward ground-state optically addressable molecular spin qubits, we exemplify how our symmetry-based design avoids Zeeman-induced singlet-triplet mixings, setting the scene for realizing electron spin qubit gates.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 1","pages":"116-126"},"PeriodicalIF":12.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044843","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}

引用次数: 0

Nickel(II)/Salox-Catalyzed Enantioselective C-H Functionalization. 镍（II）/萨洛催化的对映体选择性 C-H 功能化。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-01-02 eCollection Date: 2025-01-22 DOI: 10.1021/acscentsci.4c02049

Jia-Hao Chen, Qi-Jun Yao, Ming-Yu Zhong, Tian-Yu Jiang, Fan-Rui Huang, Xiang Li, Bing-Feng Shi

{"title":"Nickel(II)/Salox-Catalyzed Enantioselective C-H Functionalization.","authors":"Jia-Hao Chen, Qi-Jun Yao, Ming-Yu Zhong, Tian-Yu Jiang, Fan-Rui Huang, Xiang Li, Bing-Feng Shi","doi":"10.1021/acscentsci.4c02049","DOIUrl":"10.1021/acscentsci.4c02049","url":null,"abstract":"Recently, nickel catalysts have garnered considerable attention for their efficacy and versatility in asymmetric catalysis, attributed to their distinctive properties. However, the use of cost-effective and sustainable divalent nickel catalysts in C-H activation/asymmetric alkene insertion poses significant challenges due to the intricate control of stereochemistry in the transformation of the tetracoordinate C-Ni(II) intermediate. Herein, we report a Ni(II)-catalyzed enantioselective C-H/N-H annulation with oxabicyclic alkenes. This protocol offers straightforward access to chiral [2,2,1]-bridged bicyclic compounds bearing four consecutive stereocenters with high enantioselectivity (up to 96% ee). The development of a sterically hindered chiral salicyloxazoline (Salox) ligand, TMS-Salox, is key to the success of this protocol. Mechanistic investigations unveiled that a chiral Ni(III)-metalacyclic intermediate was formed through the in situ oxidation of achiral organometallic Ni(II) species and coordination of the Salox ligand. This process led to the creation of a tailored chiral pocket that guides the approach of alkenes, thereby influencing and determining the stereochemistry.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 1","pages":"127-135"},"PeriodicalIF":12.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044851","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}

引用次数: 0

Tackling Waste Polystyrene with Sunlight.

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-01-02 eCollection Date: 2025-01-22 DOI: 10.1021/acscentsci.4c02187

Hyun Suk Wang, Athina Anastasaki

引用次数: 0