ACS Combinatorial Science最新文献_第10页

IF 22.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-13 DOI: 10.1146/annurev-conmatphys-042924-103908

Anatoly Kuklov, Lode Pollet, Nikolay Prokof’ev, Boris Svistunov

引用次数: 0

Succinate dehydrogenase deficiency-driven succinate accumulation induces drug resistance in acute myeloid leukemia via ubiquitin-cullin regulation 琥珀酸脱氢酶缺乏导致的琥珀酸积累通过泛素-瓜林调控诱导急性髓性白血病的耐药性

IF 16.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-13 DOI: 10.1038/s41467-024-53398-9

Yifan Chen, Miao Xian, Wenwen Ying, Jiayi Liu, Shaowei Bing, Xiaomin Wang, Jiayi Yu, Xiaojun Xu, Senfeng Xiang, Xuejing Shao, Ji Cao, Qiaojun He, Bo Yang, Meidan Ying

{"title":"Succinate dehydrogenase deficiency-driven succinate accumulation induces drug resistance in acute myeloid leukemia via ubiquitin-cullin regulation","authors":"Yifan Chen, Miao Xian, Wenwen Ying, Jiayi Liu, Shaowei Bing, Xiaomin Wang, Jiayi Yu, Xiaojun Xu, Senfeng Xiang, Xuejing Shao, Ji Cao, Qiaojun He, Bo Yang, Meidan Ying","doi":"10.1038/s41467-024-53398-9","DOIUrl":"https://doi.org/10.1038/s41467-024-53398-9","url":null,"abstract":"Drug resistance is vital for the poor prognosis of acute myeloid leukemia (AML) patients, but the underlying mechanism remains poorly understood. Given the unique microenvironment of bone marrow, we reasoned that drug resistance of AML might rely on distinct metabolic processes. Here, we identify succinate dehydrogenase (SDH) deficiency and over-cumulative succinate as typical features in AML, with a marked function in causing the resistance of AML cells to various anti-cancer therapies. Mechanistically, succinate promotes the accumulation of oncogenic proteins in a manner that precedes transcriptional activation. This function is mediated by succinate-triggered upregulation of ubiquitin-conjugating enzyme E2M (UBC12) phosphorylation, which impairs its E2 function in cullins neddylation. Notably, decreasing succinate by fludarabine can restore the sensitivity of anti-cancer drugs in SDH-deficient AML. Together, we uncover the function of succinate in driving drug resistance by regulating p-UBC12/cullin activity, and indicate reshaping succinate metabolism as a promising treatment for SDH-deficient AML.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"2 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inductively Coupled Plasma-Mass Spectrometry (ICP-MS): An Emerging Tool in Radiopharmaceutical Science. 电感耦合等离子体质谱仪 (ICP-MS)：放射性药物科学的新兴工具。

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2024-11-13 Epub Date: 2024-10-31 DOI: 10.1021/jacs.4c12254

Karel D Klika, Jianlin Han, Marvin S Busse, Vadim A Soloshonok, Ramin Javahershenas, Frank Vanhaecke, Ata Makarem

引用次数: 0

Constructing Flexible Crystalline Porous Organic Salts via a Zwitterionic Strategy. 通过齐聚物策略构建柔性多孔有机盐晶体

IF 14.4 3区化学

ACS Combinatorial Science Pub Date : 2024-11-13 Epub Date: 2024-11-04 DOI: 10.1021/jacs.4c10713

Jin Wang, Shengyi Yang, Liang Zhang, Xuedong Xiao, Zihao Deng, Xinmeng Chen, Cheng Liu, Gongyue Huang, Ryan T K Kwok, Jacky W Y Lam, Ben Zhong Tang

{"title":"Constructing Flexible Crystalline Porous Organic Salts via a Zwitterionic Strategy.","authors":"Jin Wang, Shengyi Yang, Liang Zhang, Xuedong Xiao, Zihao Deng, Xinmeng Chen, Cheng Liu, Gongyue Huang, Ryan T K Kwok, Jacky W Y Lam, Ben Zhong Tang","doi":"10.1021/jacs.4c10713","DOIUrl":"10.1021/jacs.4c10713","url":null,"abstract":"The unique ionic channels and highly polar pore structures have distinguished crystalline porous organic salts (CPOSs) from conventional porous frameworks in the past decade. Up to now, CPOSs were all constructed by a monoionic strategy, in which two types of building units individually bearing anionic or cationic groups were introduced, thus increasing complexity in the synthesis of CPOSs. In this study, by utilizing stereoisomeric compounds of TPE-NS-Z or TPE-NS-E bearing both anionic and cationic groups as a single building unit, the zwitterionic strategy was proven feasible in constructing CPOSs. Benefiting from the single building unit, the zwitterionic strategy simplified the preparation process and reduced the difficulty in studying the aggregation behavior of building units into CPOSs. And also, this novel strategy enabled precise control of the finally obtained CPOSs through fine-tuning of the initial building units. Surprisingly, the special parallel/vertical alternated stacking mode and unique ionic interaction networks in the crystal structure provided the flexible pore characteristic of CPOS-E, which further guaranteed the multitime controllable release of highly polar chemicals in different solvents.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":" ","pages":"31042-31052"},"PeriodicalIF":14.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Whole genome CRISPRi screening identifies druggable vulnerabilities in an isoniazid resistant strain of Mycobacterium tuberculosis 全基因组 CRISPRi 筛选确定结核分枝杆菌耐异烟肼菌株中的可药用漏洞

IF 16.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-13 DOI: 10.1038/s41467-024-54072-w

XinYue Wang, William J. Jowsey, Chen-Yi Cheung, Caitlan J. Smart, Hannah R. Klaus, Noon EJ Seeto, Natalie JE Waller, Michael T. Chrisp, Amanda L. Peterson, Boatema Ofori-Anyinam, Emily Strong, Brunda Nijagal, Nicholas P. West, Jason H. Yang, Peter C. Fineran, Gregory M. Cook, Simon A. Jackson, Matthew B. McNeil

{"title":"Whole genome CRISPRi screening identifies druggable vulnerabilities in an isoniazid resistant strain of Mycobacterium tuberculosis","authors":"XinYue Wang, William J. Jowsey, Chen-Yi Cheung, Caitlan J. Smart, Hannah R. Klaus, Noon EJ Seeto, Natalie JE Waller, Michael T. Chrisp, Amanda L. Peterson, Boatema Ofori-Anyinam, Emily Strong, Brunda Nijagal, Nicholas P. West, Jason H. Yang, Peter C. Fineran, Gregory M. Cook, Simon A. Jackson, Matthew B. McNeil","doi":"10.1038/s41467-024-54072-w","DOIUrl":"https://doi.org/10.1038/s41467-024-54072-w","url":null,"abstract":"Drug-resistant strains of Mycobacterium tuberculosis are a major global health problem. Resistance to the front-line antibiotic isoniazid is often associated with mutations in the katG-encoded bifunctional catalase-peroxidase. We hypothesise that perturbed KatG activity would generate collateral vulnerabilities in isoniazid-resistant katG mutants, providing potential pathway targets to combat isoniazid resistance. Whole genome CRISPRi screens, transcriptomics, and metabolomics were used to generate a genome-wide map of cellular vulnerabilities in an isoniazid-resistant katG mutant strain of M. tuberculosis. Here, we show that metabolic and transcriptional remodelling compensates for the loss of KatG but in doing so generates vulnerabilities in respiration, ribosome biogenesis, and nucleotide and amino acid metabolism. Importantly, these vulnerabilities are more sensitive to inhibition in an isoniazid-resistant katG mutant and translated to clinical isolates. This work highlights how changes in the physiology of drug-resistant strains generates druggable vulnerabilities that can be exploited to improve clinical outcomes.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"34 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene-Directed In Vitro Mining Uncovers the Insect-Repellent Constituent from Mugwort (Artemisia argyi). 基因导向体外挖掘发现艾蒿中的驱虫成分

IF 14.4 3区化学

ACS Combinatorial Science Pub Date : 2024-11-13 Epub Date: 2024-11-01 DOI: 10.1021/jacs.4c08857

Yao Zhi, Chong Dai, Xueting Fang, Xiaochun Xiao, Hui Lu, Fangfang Chen, Rong Chen, Weihua Ma, Zixin Deng, Li Lu, Tiangang Liu

{"title":"Gene-Directed In Vitro Mining Uncovers the Insect-Repellent Constituent from Mugwort (Artemisia argyi).","authors":"Yao Zhi, Chong Dai, Xueting Fang, Xiaochun Xiao, Hui Lu, Fangfang Chen, Rong Chen, Weihua Ma, Zixin Deng, Li Lu, Tiangang Liu","doi":"10.1021/jacs.4c08857","DOIUrl":"10.1021/jacs.4c08857","url":null,"abstract":"Plants contain a vast array of natural products yet to be discovered, particularly those minor bioactive constituents. Identification of these constituents requires a significant amount of plant material, presenting considerable technical challenges. Mugwort (Artemisia argyi) is a widely recognized insect repellent herb, particularly renowned for its extensive usage during the Dragon Boat Festival in China, but the specific constituent responsible for its repellent activity remains unknown. Here, we employed a gene-directed in vitro mining approach to characterize mugwort terpene synthases (TPSs) systematically in a yeast expression system. Based on the establishment of \"Terpene synthase-standard library\", we have successfully identified 54 terpene products, including a novel compound designated as cyclosantalol. Through activity screening, we have identified that (+)-intermedeol, which presents in trace amount in plants, exhibits significant repellent activity against mosquitoes and ticks. After establishing its safety and efficacy, we then achieved its biosynthetic production in a yeast chassis, with an initial yield of 2.34 g/L. The methodology employed in this study not only identified a highly effective, safe, and commercially viable insect repellent derived from mugwort but also holds promise for uncovering and producing other valuable plant natural products in future research endeavors.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":" ","pages":"30883-30892"},"PeriodicalIF":14.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Programmable Piperazine Synthesis via Organic Photoredox Catalysis. 通过有机光氧化催化合成可编程哌嗪。

IF 14.4 3区化学

ACS Combinatorial Science Pub Date : 2024-11-13 Epub Date: 2024-11-01 DOI: 10.1021/jacs.4c12028

Alexander J Boley, Jason C Genova, David A Nicewicz

引用次数: 0

Electrochemical Synthesis of Nitrite and Nitrate via Cathodic Oxygen Activation in Liquefied Ammonia. 在液化氨中通过阴极氧活化电化学合成亚硝酸盐和硝酸盐。

IF 3.784 3区化学

ACS Combinatorial Science Pub Date : 2024-11-13 Epub Date: 2024-11-04 DOI: 10.1021/jacs.4c10279

Moritz Lukas Krebs, Ferdi Schüth

引用次数: 0

Ruthenium-Substituted Polyoxoanion Serves as Redox Shuttle and Intermediate Stabilizer in Selective Electrooxidation of Ethylene to Ethylene Glycol 钌取代的多氧阴离子在乙烯到乙二醇的选择性电氧化过程中充当氧化还原梭子和中间稳定剂

IF 15 3区化学

ACS Combinatorial Science Pub Date : 2024-11-13 DOI: 10.1021/jacs.4c11891

Jiaqi Yu, Charles Bruce Musgrave, III, Qiucheng Chen, Yi Yang, Cong Tian, Xiaobing Hu, Guangcan Su, Heejong Shin, Weiyan Ni, Xinqi Chen, Pengfei Ou, Yuan Liu, Neil M. Schweitzer, Debora Motta Meira, Vinayak P. Dravid, William A. Goddard, III, Ke Xie, Edward H. Sargent

{"title":"Ruthenium-Substituted Polyoxoanion Serves as Redox Shuttle and Intermediate Stabilizer in Selective Electrooxidation of Ethylene to Ethylene Glycol","authors":"Jiaqi Yu, Charles Bruce Musgrave, III, Qiucheng Chen, Yi Yang, Cong Tian, Xiaobing Hu, Guangcan Su, Heejong Shin, Weiyan Ni, Xinqi Chen, Pengfei Ou, Yuan Liu, Neil M. Schweitzer, Debora Motta Meira, Vinayak P. Dravid, William A. Goddard, III, Ke Xie, Edward H. Sargent","doi":"10.1021/jacs.4c11891","DOIUrl":"https://doi.org/10.1021/jacs.4c11891","url":null,"abstract":"The high carbon intensity of present-day ethylene glycol (EG) production motivates interest in electrifying ethylene oxidation. Noting poor kinetics in prior reports of the organic electrooxidation of small hydrocarbons, we explored the design of mediators that activate and simultaneously stabilize light alkenes. A ruthenium-substituted polyoxometalate (Ru-POM, {Si[Ru(H2O)W11O39]}5–) achieves 82% faradaic efficiency in EG production at 100 mA/cm2 under ambient conditions. Via the union of in situ spectroscopic techniques, electrochemical studies, and density functional theory calculations, we find evidence of a two-step oxidation mechanism: Ru-POM first undergoes electrochemical oxidation to the high valent state, activating ethylene via partial oxidation and forming an intermediate complex; this intermediate complex then migrates to the anode where it undergoes further oxidation to produce EG. The Ru-POM-mediated electrocatalytic system reduces the projected energy consumption required in EG production, requiring 9 GJ per ton of EG (and accompanied by 0.04 ton H2 coproduction), compared to 20–30 GJ/ton in typical prior processes.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"17 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

General Alkene 1,2-syn-Cyano-Hydroxylation Procedure Via Electrochemical Activation of Isoxazoline Cycloadducts 通过异噁唑啉环加载物的电化学活化实现烯烃 1,2-氰基-羟基化的一般步骤

IF 15 3区化学

ACS Combinatorial Science Pub Date : 2024-11-13 DOI: 10.1021/jacs.4c13682

Taciano A. S. Wanderley, Roberto Buscemi, Órla Conboy, Benjamin Knight, Giacomo E. M. Crisenza

{"title":"General Alkene 1,2-syn-Cyano-Hydroxylation Procedure Via Electrochemical Activation of Isoxazoline Cycloadducts","authors":"Taciano A. S. Wanderley, Roberto Buscemi, Órla Conboy, Benjamin Knight, Giacomo E. M. Crisenza","doi":"10.1021/jacs.4c13682","DOIUrl":"https://doi.org/10.1021/jacs.4c13682","url":null,"abstract":"Stereoselective alkene 1,2-difunctionalization is a privileged strategy to access three-dimensional C(sp3)-rich chiral molecules from readily available “flat” carbon feedstocks. State-of-the-art approaches exploit chiral transition metal-catalysts to enable high levels of regio- and stereocontrol. However, this is often achieved at the expense of a limited alkene scope and reduced generality. 1,3-Dipolar cycloadditions are routinely used to form heterocycles from alkenes with high levels of regioselectivity and stereospecificity. Nevertheless, methods for the ring-opening of cycloadducts to reveal synthetically useful functionalities require the use of hazardous reagents or forcing reaction conditions; thus limiting their synthetic applications. Herein, we describe the implementation of a practical, general and selective electrosynthetic strategy for olefin 1,2-syn-difunctionalization, which hinges on the design of novel reagents–consisting of a nitrile oxide 1,3-dipole precursor, equipped with a sulfonyl-handle. These can selectively difunctionalize alkenes via “click” 1,3-dipolar cycloadditions, and then facilitate the telescoped electrochemical single electron transfer activation of the ensuing isoxazoline intermediate. Cathodic reduction of the cycloadduct triggers a radical fragmentation pathway delivering sought-after stereodefined 1,2-syn-hydroxy nitrile derivatives. Our telescoped electrochemical procedure tolerates a wide range of functionalities, and─crucially─enables the difunctionalization of both electron-rich, electron-poor and unactivated olefins, with diverse degree of substitution; thus providing a robust, general and selective metal-free alternative to current alkene difunctionalization strategies. Capitalizing on these features, we employed our electrosynthetic method to enable the late-stage syn-hydroxy-cyanation of natural products and bioactive compounds, and streamline the de novo synthesis of pharmaceutical agents.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"20 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0