JACS Au最新文献 - Book学术

Announcing the Winner of the 2024 JACS Au Outstanding Paper Award 宣布 2024 年度江淮科苑杰出论文奖得主

IF 8.5

JACS Au Pub Date : 2024-10-28 DOI: 10.1021/jacsau.4c0095610.1021/jacsau.4c00956

Christopher W. Jones*,

引用次数: 0

Announcing the Winner of the 2024 JACS Au Outstanding Paper Award. 宣布 2024 年 JACS Au 优秀论文奖得主。

IF 8.5

JACS Au Pub Date : 2024-10-28 DOI: 10.1021/jacsau.4c00956

Christopher W Jones

引用次数: 0

Poly-Dha Sequences as Pro-polypeptides: An Original Mechanistic Postulate Leads to the Discovery of a Long-Acting Vasodilator KU04212 作为原多肽的聚-Dha 序列：原创机制推测导致发现长效血管扩张剂 KU04212

IF 8.5

JACS Au Pub Date : 2024-10-07 DOI: 10.1021/jacsau.4c0060310.1021/jacsau.4c00603

Allen Alonso Haysom-Rodríguez, and , Steven Bloom*,

{"title":"Poly-Dha Sequences as Pro-polypeptides: An Original Mechanistic Postulate Leads to the Discovery of a Long-Acting Vasodilator KU04212","authors":"Allen Alonso Haysom-Rodríguez,  and , Steven Bloom*, ","doi":"10.1021/jacsau.4c0060310.1021/jacsau.4c00603","DOIUrl":"https://doi.org/10.1021/jacsau.4c00603https://doi.org/10.1021/jacsau.4c00603","url":null,"abstract":"The construction of polypeptides was revolutionized by Merrifield’s solid-phase synthesis more than half a century ago. Herein, we explore a completely different approach to making peptides. We test an original mechanistic postulate wherein a single peptide made entirely of dehydroalanine (Dha) residues can give rise to regio- and stereodefined peptides by iterative conjugate addition of one- or two-electron nucleophiles. Each nucleophile appends a unique amino acid side chain to the peptide backbone. We show that side chain addition is not random. Side chains are added in one of two ways, in an electrophilicity-gated fashion (most cases) or in a substrate-directed manner, depending on the first nucleophile used in the synthesis. One peptide made in this series, KU04212, a first-in-class polyazole peptide, was found to reduce vascular length density (−17%; p < 0.05) and increase vessel diameter (124%; p < 0.001) in healthy day 6 chick embryos at 24 h post-single dose. It also rescued 75% of the embryos administered a 32-fold lethal dose of ischemia-inducing CoCl2 after 12 h and 12.5% of the embryos after 24 h. In comparison to three mechanistically distinct vasodilators, e.g., isosorbide mononitrate, amlodipine besylate, and prazosin, only KU04212 showed long-acting effects in vivo, making it an enticing lead for the treatment of ischemic disorders.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142550429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pyrimidine Azepine Targets the Plasmodium bc ₁ Complex and Displays Multistage Antimalarial Activity. 嘧啶氮杂环庚烷以疟原虫 bc 1 复合物为靶标，发挥多级抗疟活性

IF 8.5

JACS Au Pub Date : 2024-10-07 eCollection Date: 2024-10-28 DOI: 10.1021/jacsau.4c00674

Juliana Calit, Surendra K Prajapati, Ernest D Benavente, Jessica E Araújo, Bingbing Deng, Kazutoyo Miura, Yasmin Annunciato, Igor M R Moura, Miho Usui, Jansen F Medeiros, Carolina H Andrade, Sabrina Silva-Mendonça, Anton Simeonov, Richard T Eastman, Carole A Long, Maisa da Silva Araujo, Kim C Williamson, Anna Caroline C Aguiar, Daniel Y Bargieri

{"title":"Pyrimidine Azepine Targets the Plasmodium bc 1 Complex and Displays Multistage Antimalarial Activity.","authors":"Juliana Calit, Surendra K Prajapati, Ernest D Benavente, Jessica E Araújo, Bingbing Deng, Kazutoyo Miura, Yasmin Annunciato, Igor M R Moura, Miho Usui, Jansen F Medeiros, Carolina H Andrade, Sabrina Silva-Mendonça, Anton Simeonov, Richard T Eastman, Carole A Long, Maisa da Silva Araujo, Kim C Williamson, Anna Caroline C Aguiar, Daniel Y Bargieri","doi":"10.1021/jacsau.4c00674","DOIUrl":"10.1021/jacsau.4c00674","url":null,"abstract":"Malaria control and elimination efforts would benefit from the identification and validation of new malaria chemotherapeutics. Recently, a transgenic Plasmodium berghei line was used to perform a series of high-throughput in vitro screens for new antimalarials acting against the parasite sexual stages. The screens identified pyrimidine azepine chemotypes with potent activity. Here, we validate the activity of PyAz90, the most potent pyrimidine azepine chemotype identified, against P. falciparum and P. vivax in the asexual and sexual stages. PyAz90 blocked parasite transmission to the mosquito vector at nanomolar concentrations and inhibited in vitro asexual parasite multiplication with a fast-action profile. Through the generation of P. falciparum PyAz90-resistant parasites and in vitro assays of mitochondrial activity, we identified cytochrome b as a molecular target of PyAz90. This work characterizes a promising chemotype that can be explored for the future development of new antimalarials targeting the Plasmodium cytochrome bc 1 complex.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Weak Base-Promoted Direct Cross-Coupling of Naphthalene-1,8-diaminato-substituted Arylboron Compounds 弱碱促进萘-1,8-二氨基取代芳基硼化合物的直接交叉偶联

IF 8.5

JACS Au Pub Date : 2024-10-07 DOI: 10.1021/jacsau.4c0066510.1021/jacsau.4c00665

Kazuki Tomota, Jialun Li, Hideya Tanaka, Masaaki Nakamoto, Takumi Tsushima and Hiroto Yoshida*,

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引用次数: 0

Pyrimidine Azepine Targets the Plasmodium bc1 Complex and Displays Multistage Antimalarial Activity 嘧啶氮杂环庚烷靶向疟原虫 bc1 复合物并显示多级抗疟活性

IF 8.5

JACS Au Pub Date : 2024-10-07 DOI: 10.1021/jacsau.4c0067410.1021/jacsau.4c00674

Juliana Calit, Surendra K. Prajapati, Ernest D. Benavente, Jessica E. Araújo, Bingbing Deng, Kazutoyo Miura, Yasmin Annunciato, Igor M. R. Moura, Miho Usui, Jansen F. Medeiros, Carolina H. Andrade, Sabrina Silva-Mendonça, Anton Simeonov, Richard T. Eastman, Carole A. Long, Maisa da Silva Araujo, Kim C. Williamson, Anna Caroline C. Aguiar* and Daniel Y. Bargieri*,

{"title":"Pyrimidine Azepine Targets the Plasmodium bc1 Complex and Displays Multistage Antimalarial Activity","authors":"Juliana Calit, Surendra K. Prajapati, Ernest D. Benavente, Jessica E. Araújo, Bingbing Deng, Kazutoyo Miura, Yasmin Annunciato, Igor M. R. Moura, Miho Usui, Jansen F. Medeiros, Carolina H. Andrade, Sabrina Silva-Mendonça, Anton Simeonov, Richard T. Eastman, Carole A. Long, Maisa da Silva Araujo, Kim C. Williamson, Anna Caroline C. Aguiar* and Daniel Y. Bargieri*, ","doi":"10.1021/jacsau.4c0067410.1021/jacsau.4c00674","DOIUrl":"https://doi.org/10.1021/jacsau.4c00674https://doi.org/10.1021/jacsau.4c00674","url":null,"abstract":"Malaria control and elimination efforts would benefit from the identification and validation of new malaria chemotherapeutics. Recently, a transgenic Plasmodium berghei line was used to perform a series of high-throughput in vitro screens for new antimalarials acting against the parasite sexual stages. The screens identified pyrimidine azepine chemotypes with potent activity. Here, we validate the activity of PyAz90, the most potent pyrimidine azepine chemotype identified, against P. falciparum and P. vivax in the asexual and sexual stages. PyAz90 blocked parasite transmission to the mosquito vector at nanomolar concentrations and inhibited in vitro asexual parasite multiplication with a fast-action profile. Through the generation of P. falciparum PyAz90-resistant parasites and in vitro assays of mitochondrial activity, we identified cytochrome b as a molecular target of PyAz90. This work characterizes a promising chemotype that can be explored for the future development of new antimalarials targeting the Plasmodium cytochrome bc1 complex.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00674","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142517200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Poly-Dha Sequences as Pro-polypeptides: An Original Mechanistic Postulate Leads to the Discovery of a Long-Acting Vasodilator KU04212. 作为原多肽的聚-Dha 序列：一种原创性机制假设导致发现长效血管扩张剂 KU04212。

IF 8.5

JACS Au Pub Date : 2024-10-07 eCollection Date: 2024-10-28 DOI: 10.1021/jacsau.4c00603

Allen Alonso Haysom-Rodríguez, Steven Bloom

{"title":"Poly-Dha Sequences as Pro-polypeptides: An Original Mechanistic Postulate Leads to the Discovery of a Long-Acting Vasodilator KU04212.","authors":"Allen Alonso Haysom-Rodríguez, Steven Bloom","doi":"10.1021/jacsau.4c00603","DOIUrl":"10.1021/jacsau.4c00603","url":null,"abstract":"The construction of polypeptides was revolutionized by Merrifield's solid-phase synthesis more than half a century ago. Herein, we explore a completely different approach to making peptides. We test an original mechanistic postulate wherein a single peptide made entirely of dehydroalanine (Dha) residues can give rise to regio- and stereodefined peptides by iterative conjugate addition of one- or two-electron nucleophiles. Each nucleophile appends a unique amino acid side chain to the peptide backbone. We show that side chain addition is not random. Side chains are added in one of two ways, in an electrophilicity-gated fashion (most cases) or in a substrate-directed manner, depending on the first nucleophile used in the synthesis. One peptide made in this series, KU04212, a first-in-class polyazole peptide, was found to reduce vascular length density (-17%; p < 0.05) and increase vessel diameter (124%; p < 0.001) in healthy day 6 chick embryos at 24 h post-single dose. It also rescued 75% of the embryos administered a 32-fold lethal dose of ischemia-inducing CoCl2 after 12 h and 12.5% of the embryos after 24 h. In comparison to three mechanistically distinct vasodilators, e.g., isosorbide mononitrate, amlodipine besylate, and prazosin, only KU04212 showed long-acting effects in vivo, making it an enticing lead for the treatment of ischemic disorders.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Weak Base-Promoted Direct Cross-Coupling of Naphthalene-1,8-diaminato-substituted Arylboron Compounds. 弱碱促进的萘-1,8-二氨基取代芳基硼化合物的直接交叉偶联。

IF 8.5

JACS Au Pub Date : 2024-10-07 eCollection Date: 2024-10-28 DOI: 10.1021/jacsau.4c00665

Kazuki Tomota, Jialun Li, Hideya Tanaka, Masaaki Nakamoto, Takumi Tsushima, Hiroto Yoshida

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引用次数: 0

A Self-Immobilizing Photosensitizer with Long-Term Retention for Hypoxia Imaging and Enhanced Photodynamic Therapy. 用于缺氧成像和增强型光动力疗法的可长期保留的自固定光敏剂。

IF 8.5

JACS Au Pub Date : 2024-10-03 eCollection Date: 2024-10-28 DOI: 10.1021/jacsau.4c00787

Zifan Zhu, Yun Feng, Qiufen Tian, Jiawen Li, Chencong Liu, Yuchi Cheng, Sanjun Zhang, Yijing Dang, Jing Gao, Yi Lai, Fan Zhang, Haijun Yu, Wen Zhang, Zhiai Xu

{"title":"A Self-Immobilizing Photosensitizer with Long-Term Retention for Hypoxia Imaging and Enhanced Photodynamic Therapy.","authors":"Zifan Zhu, Yun Feng, Qiufen Tian, Jiawen Li, Chencong Liu, Yuchi Cheng, Sanjun Zhang, Yijing Dang, Jing Gao, Yi Lai, Fan Zhang, Haijun Yu, Wen Zhang, Zhiai Xu","doi":"10.1021/jacsau.4c00787","DOIUrl":"10.1021/jacsau.4c00787","url":null,"abstract":"The precise theranostic strategy of fluorescence imaging-guided photodynamic therapy (PDT) can effectively mitigate the adverse effect of photosensitizers in normal cells and tissues. However, low tumor enrichment and high diffusivity of photosensitizers significantly compromise the imaging accuracy and PDT effect. In this study, we have developed a nitroreductase (NTR)-activated and self-immobilizing photosensitizer CyNT-F, which showed enhanced enrichment in tumor tissues and facilitated precise and sustained imaging as well as PDT for hypoxia tumors. mPEG-b-PDPA nanomicelles encapsulating photosensitizers underwent dissociation and released CyNT-F in tumor cells. CyNT-F and NTR enzymatically reacted in situ to generate highly reactive quinone methide, subsequently covalently binding to adjacent proteins for fluorescence and PDT activation. CyNT-F exhibited longer intracellular retention (7 days) and effectively inhibited the tumor growth of solid hypoxia tumor. We believe the activatable and self-immobilizing strategy of PDT presents a novel methodology for minimizing the adverse effect and enabling spatiotemporally accurate ablation of diseased cells and tissues.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Eutectogels: The Multifaceted Soft Ionic Materials of Tomorrow. 共晶凝胶：未来的多元软离子材料。

IF 8.5

JACS Au Pub Date : 2024-10-03 eCollection Date: 2024-10-28 DOI: 10.1021/jacsau.4c00677

Pablo A Mercadal, Agustín González, Ana Beloqui, Liliana C Tomé, David Mecerreyes, Marcelo Calderón, Matias L Picchio

{"title":"Eutectogels: The Multifaceted Soft Ionic Materials of Tomorrow.","authors":"Pablo A Mercadal, Agustín González, Ana Beloqui, Liliana C Tomé, David Mecerreyes, Marcelo Calderón, Matias L Picchio","doi":"10.1021/jacsau.4c00677","DOIUrl":"10.1021/jacsau.4c00677","url":null,"abstract":"Eutectogels, a rising category of soft materials, have recently garnered significant attention owing to their remarkable potential in various domains. This innovative class of materials consists of a eutectic solvent immobilized in a three-dimensional network structure. The use of eco-friendly and cost-effective eutectic solvents further emphasizes the appeal of these materials in multiple applications. Eutectogels exhibit key characteristics of most eutectic solvents, including environmental friendliness, facile preparation, low vapor pressure, and good ionic conductivity. Moreover, they can be tailored to display functionalities such as self-healing capability, adhesiveness, and antibacterial properties, which are facilitated by incorporating specific combinations of the eutectic mixture constituents. This perspective article delves into the current landscape and challenges associated with eutectogels, particularly focusing on their potential applications in CO2 separation, drug delivery systems, battery technologies, biocatalysis, and food packaging. By exploring these diverse realms, we aim to shed light on the transformative capabilities of eutectogels and the opportunities they present to address pressing industrial, academic, and environmental challenges.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0