Journal of the American Chemical Society最新文献_第3页

G3BP1/2-Targeting PROTAC Disrupts Stress Granules Dependent ATF4 Migracytosis as Cancer Therapy

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2024-12-22 DOI: 10.1021/jacs.4c11146

Ting Dong, Fabao Zhao, Mengmeng Wang, Kaige Lyu, Jiayu Zhu, Wenru Zhang, Wenzhe Li, Yixuan An, Na Liu, Akhand Pratap Singh, Yue Yang, Dongwei Kang, Xiaohui Liu

{"title":"G3BP1/2-Targeting PROTAC Disrupts Stress Granules Dependent ATF4 Migracytosis as Cancer Therapy","authors":"Ting Dong, Fabao Zhao, Mengmeng Wang, Kaige Lyu, Jiayu Zhu, Wenru Zhang, Wenzhe Li, Yixuan An, Na Liu, Akhand Pratap Singh, Yue Yang, Dongwei Kang, Xiaohui Liu","doi":"10.1021/jacs.4c11146","DOIUrl":"https://doi.org/10.1021/jacs.4c11146","url":null,"abstract":"Stress granules (SGs) are membraneless cytoplasmic compartments that form in response to stress stimuli. In these compartments, most translation factors stall, except for activating transcription factor 4 (ATF4), which is preferentially translated to ensure cell survival under stressful conditions. Cancer cells encounter various stress conditions in the tumor microenvironment during tumorigenesis; however, how they exploit the pro-survival effects of ATF4 in SGs remains unclear. G3BP1/2 are central nodes of the SG network, regulating SG dynamics. In this study, we designed two small molecules, #129 and PROTAC (Proteolysis Targeting Chimera) degrader 129 (PT-129), which specifically target the NTF2L domain of G3BP1/2, a crucial hub for protein and RNA interactions. These compounds inhibit the formation of stress granules in stressed cells and disassemble pre-existing stress granules. Furthermore, pharmacological inhibition by PT-129 suppressed fibroblast-mediated cancer cell growth in vitro and reduced tumor growth in vivo. Mechanistically, SG facilitates the delivery of ATF4 from fibroblasts to tumor cells via migracytosis, a primary mediator of fibroblast-associated tumor growth. PT-129-mediated disassembly of stress granules disrupts ATF4 delivery, thereby preventing cancer cell proliferation. These compounds, therefore, represent powerful tools for gaining molecular insights into SGs and hold promise for cancer therapeutic interventions by modulating stress granule dynamics.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"111 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Correction to “Direct Measurements of Covalently Bonded Sulfuric Anhydrides from Gas-Phase Reactions of SO3 with Acids under Ambient Conditions”

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2024-12-22 DOI: 10.1021/jacs.4c16560

Avinash Kumar, Siddharth Iyer, Shawon Barua, James Brean, Emin Besic, Prasenjit Seal, Manuel Dall’Osto, David C. S. Beddows, Nina Sarnela, Tuija Jokinen, Mikko Sipilä, Roy M. Harrison, Matti Rissanen

引用次数: 0

What Is the “Other” Site in M–N–C?

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2024-12-21 DOI: 10.1021/jacs.4c12479

Zachary Levell, Saerom Yu, Ruoyu Wang, Yuanyue Liu

引用次数: 0

Facile Synthesis of Functional Polytrithiocarbonates from Multicomponent Tandem Polymerizations of CS2, Thiols, and Alkyl Halides 从 CS2、硫醇和烷基卤化物的多组分串联聚合反应中简便合成功能性聚三硫代碳酸酯

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2024-12-21 DOI: 10.1021/jacs.4c14708

Longbin Chen, Rongrong Hu, Ben Zhong Tang

{"title":"Facile Synthesis of Functional Polytrithiocarbonates from Multicomponent Tandem Polymerizations of CS2, Thiols, and Alkyl Halides","authors":"Longbin Chen, Rongrong Hu, Ben Zhong Tang","doi":"10.1021/jacs.4c14708","DOIUrl":"https://doi.org/10.1021/jacs.4c14708","url":null,"abstract":"Polytrithiocarbonates have attracted significant attention recently because of their good thermal stability, light refractivity, crystallinity, and mechanical properties; however, the exploration of their structures and functionalities has been limited by their synthetic approaches. Multicomponent polymerization featuring simple monomers, mild conditions, diversified product structures, and high efficiency could provide a powerful and versatile tool to synthesize various polytrithiocarbonates from commercially available monomers. Herein, a robust and efficient multicomponent tandem polymerization (MCTP) of CS2, dithiols, and alkyl halides was developed in DMF with K2CO3 at room temperature in air to synthesize 12 polytrithiocarbonates with diversified and systematically tuned structures, high molecular weights (Mns up to 37900 g/mol), and high yields (up to 93%). Depending on the different polymer backbone structures, amorphous polytrithiocarbonates showed excellent breaking elongations, and crystallinic polytrithiocarbonates possessed a large process temperature window (about 200 °C) and good mechanical performance (σB of 23.6 MPa and εB of 858%), whose tensile strength could be dramatically enhanced to 87.5 MPa after uniaxial extension deformation. The upper critical solution temperature (UCST) in organic solvents, together with nonconventional luminescence, were observed for the crystallinic polytrithiocarbonates, even without any aromatic ring. This efficient, robust, mild, and economic MCTP of CS2 thus opened up an avenue for the facile construction of polytrithiocarbonates with structural diversity, bringing modulable mechanical, thermal, luminescent, and thermal-responsive properties, which would greatly broaden the scope of structures and applications of sulfur-containing polymers.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"88 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Parallel Proteomic and Transcriptomic Microenvironment Mapping (μMap) of Nuclear Condensates in Living Cells

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2024-12-21 DOI: 10.1021/jacs.4c11612

Steve D. Knutson, Chenmengxiao Roderick Pan, Niels Bisballe, Brandon J. Bloomer, Philip Raftopolous, Iakovos Saridakis, David W. C. MacMillan

{"title":"Parallel Proteomic and Transcriptomic Microenvironment Mapping (μMap) of Nuclear Condensates in Living Cells","authors":"Steve D. Knutson, Chenmengxiao Roderick Pan, Niels Bisballe, Brandon J. Bloomer, Philip Raftopolous, Iakovos Saridakis, David W. C. MacMillan","doi":"10.1021/jacs.4c11612","DOIUrl":"https://doi.org/10.1021/jacs.4c11612","url":null,"abstract":"Cellular activity is spatially organized across different organelles. While several structures are well-characterized, many organelles have unknown roles. Profiling biomolecular composition is key to understanding function but is difficult to achieve in the context of small, dynamic structures. Photoproximity labeling has emerged as a powerful tool for mapping these interaction networks, yet maximizing catalyst localization and reducing toxicity remains challenging in live cell applications. Here, we disclose a new intracellular photocatalyst with minimal cytotoxicity and off-target binding, and we utilize this catalyst for HaloTag-based microenvironment-mapping (μMap) to spatially catalog subnuclear condensates in living cells. We also specifically develop a novel RNA-focused workflow (μMap-seq) to enable parallel transcriptomic and proteomic profiling of these structures. After validating the accuracy of our approach, we generate a spatial map across the nucleolus, nuclear lamina, Cajal bodies, paraspeckles, and PML bodies. These results provide potential new insights into RNA metabolism and gene regulation while significantly expanding the μMap platform for improved live-cell proximity labeling in biological systems.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"40 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Copper-Catalyzed Cyclization and Alkene Transposition Cascade Enables a Modular Synthesis of Complex Spirocyclic Ethers

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2024-12-20 DOI: 10.1021/jacs.4c14418

Wan-Xu Wei, Yangjin Kuang, Martin Tomanik

{"title":"Copper-Catalyzed Cyclization and Alkene Transposition Cascade Enables a Modular Synthesis of Complex Spirocyclic Ethers","authors":"Wan-Xu Wei, Yangjin Kuang, Martin Tomanik","doi":"10.1021/jacs.4c14418","DOIUrl":"https://doi.org/10.1021/jacs.4c14418","url":null,"abstract":"Complexity-generating reactions that access three-dimensional products from simple starting materials offer substantial value for drug discovery. While oxygen-containing heterocycles frequently feature unique, nonaromatic architectures such as spirocyclic rings, exploration of these chemical spaces is limited by conventional synthetic approaches. Herein, we report a copper-catalyzed annulation and alkene transposition cascade reaction that enables a modular preparation of complex, spirocyclic ethers from readily available alkenol substrates via a copper-catalyzed annulation and transannular 1,5-hydrogen atom transfer-mediated C–H functionalization. Our transformation displays a broad substrate scope, shows excellent heteroatom compatibility, and readily constructs spirocycles of varying ring sizes. The wider synthetic utility of this method is highlighted by numerous product diversifications and a short synthesis of the all-carbon framework of spirotenuipesine A. We anticipate that this transformation can significantly streamline access to a privileged class of three-dimensional oxygen-containing heterocycles and will find broad application in natural product synthesis.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"268 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

High Molecular Conductance and Inverted Conductance Decay over 3 nm in Aminium-Terminated Carbon-Bridged Oligophenylene-Vinylenes

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2024-12-20 DOI: 10.1021/jacs.4c13901

Luisa K. I. Rieger, Susanne Leitherer, William Bro-Jo̷rgensen, Gemma C. Solomon, Rainer F. Winter

{"title":"High Molecular Conductance and Inverted Conductance Decay over 3 nm in Aminium-Terminated Carbon-Bridged Oligophenylene-Vinylenes","authors":"Luisa K. I. Rieger, Susanne Leitherer, William Bro-Jo̷rgensen, Gemma C. Solomon, Rainer F. Winter","doi":"10.1021/jacs.4c13901","DOIUrl":"https://doi.org/10.1021/jacs.4c13901","url":null,"abstract":"With the progressing miniaturization of electronic device components to improve circuit density while retaining or even reducing spatial requirements, single molecules employed as electric components define the lower limit of accessible structural width. To circumvent the typical exponential conductance decay for increasing length in molecule-based wires, topological states, which describe the occurrence of discontinuities of a bulk material’s electronic structure confined to its surface, can be realized for molecules by the introduction of unpaired spins at the molecular termini. The resulting high conductance and reversed conductance decay are typically only observed for shorter molecules, as the terminal spins must be within the electronic coupling range to produce the desired effects. We expand the realm of long and exceptionally conductive molecular wires by employing highly conjugated, planarized carbon-bridged oligo(phenylene-vinylene)s as conduits between readily oxidizable diarylamine termini. This yields molecular wires of already decent conductance values and small conductance decay in the neutral state. Upon the introduction of topological states, the conductance can be increased by a factor of up to 1800 for a 3 nm long molecule, and the conductance decay becomes inverted, together with an excellent signal intensity at concentrations as low as 0.01 mM.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Enhancing Proton-Coupled Electron Transfer in Blue Light Using FAD Photoreceptor AppABLUF

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2024-12-20 DOI: 10.1021/jacs.4c11817

YongLe He, Agnieszka A. Gil, Sergey P. Laptenok, Anam Fatima, Jinnette Tolentino Collado, James N. Iuliano, Helena A. Woroniecka, Richard Brust, Aya Sabbah, Michael Towrie, Gregory M. Greetham, Igor V. Sazanovich, Jarrod B. French, Andras Lukacs, Stephen R. Meech, Peter J. Tonge

{"title":"Enhancing Proton-Coupled Electron Transfer in Blue Light Using FAD Photoreceptor AppABLUF","authors":"YongLe He, Agnieszka A. Gil, Sergey P. Laptenok, Anam Fatima, Jinnette Tolentino Collado, James N. Iuliano, Helena A. Woroniecka, Richard Brust, Aya Sabbah, Michael Towrie, Gregory M. Greetham, Igor V. Sazanovich, Jarrod B. French, Andras Lukacs, Stephen R. Meech, Peter J. Tonge","doi":"10.1021/jacs.4c11817","DOIUrl":"https://doi.org/10.1021/jacs.4c11817","url":null,"abstract":"The Blue Light Using FAD (BLUF) photoreceptor utilizes a noncovalently bound FAD to absorb light and trigger the initial ultrafast events in receptor activation. FAD undergoes 1 and 2 electron reduction as an enzyme redox cofactor, and studies on the BLUF photoreceptor PixD revealed the formation of flavin radicals (FAD•– and FADH•) during the photocycle, supporting a general mechanism for BLUF operation that involves PCET from a conserved Tyr to the oxidized FAD. However, no radical intermediates are observed in the closely related BLUF proteins AppABLUF and BlsA, and replacing the conserved Tyr with fluoro-Tyr analogs that increase the acidity of the phenol OH has a minor effect on AppABLUF photoactivation in contrast to PixD where the photocycle is halted at FAD•–. The hydrogen bonding network in BLUF proteins contains several strictly conserved residues but differs in the identity of amino acids that interact with the flavin C2═O. In PixD there are two hydrogen bonds to the C2═O, whereas there is only one in AppABLUF. Using TRIR we show that the introduction of a second hydrogen bond to the C2═O in AppABLUF results in the formation of flavin radicals (FAD•– and FADH•) during the photocycle. Subsequent replacement of the conserved Tyr (Y21) in the double mutant with 2,3,5-trifluoroTyr prevents radical formation and generation of the light state, indicating that the AppABLUF photocycle is now similar to that of PixD. The ability to trigger PCET provides fundamental insight into the role of electron transfer in the mechanism of BLUF photoactivation.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"78 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Optimally Miscible Polymer Bulk-Heterojunction-Particles for Nonsurfactant Photocatalytic Hydrogen Evolution

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2024-12-20 DOI: 10.1021/jacs.4c13856

Wei-Cheng Lin, Yu-En Sun, Ying-Rang Zhuang, Tse-Fu Huang, Kuei-Jhong Lin, Mohamed M. Elsenety, Jui-Chen Yen, Hung-Kai Hsu, Bo-Han Chen, Chen-Yu Chang, Je-Wei Chang, Hsin-Ni Huang, Bing-Heng Li, Siriporn Jungsuttiwong, Toton Haldar, Shin-Huei Wang, Wan-Chi Lin, Tien-Lin Wu, Chin-Wen Chen, Chi-Hua Yu, An-Chung Su, Kun-Han Lin, U-Ser Jeng, Shang-Da Yang, Ho-Hsiu Chou

{"title":"Optimally Miscible Polymer Bulk-Heterojunction-Particles for Nonsurfactant Photocatalytic Hydrogen Evolution","authors":"Wei-Cheng Lin, Yu-En Sun, Ying-Rang Zhuang, Tse-Fu Huang, Kuei-Jhong Lin, Mohamed M. Elsenety, Jui-Chen Yen, Hung-Kai Hsu, Bo-Han Chen, Chen-Yu Chang, Je-Wei Chang, Hsin-Ni Huang, Bing-Heng Li, Siriporn Jungsuttiwong, Toton Haldar, Shin-Huei Wang, Wan-Chi Lin, Tien-Lin Wu, Chin-Wen Chen, Chi-Hua Yu, An-Chung Su, Kun-Han Lin, U-Ser Jeng, Shang-Da Yang, Ho-Hsiu Chou","doi":"10.1021/jacs.4c13856","DOIUrl":"https://doi.org/10.1021/jacs.4c13856","url":null,"abstract":"Mini-emulsion and nanoprecipitation techniques relied on large amounts of surfactants, and unresolved miscibility issues of heterojunction materials limited their efficiency and applicability in the past. Through our molecular design and developed surfactant-free precipitation method, we successfully fabricated the best miscible bulk-heterojunction-particles (BHJP) ever achieved, using donor (PS) and acceptor (PSOS) polymers. The structural similarity ensures optimal miscibility, as supported by the interaction parameter of the PS/PSOS blend is positioned very close to the binodal curve. Experimental studies and molecular dynamics simulations further revealed that surfactants hinder electron output sites and reduce the concentration of sacrificial agents at the interface, slowing polaron formation. Multiscale experiments verified that these BHJP, approximately 12 nm in diameter, further form cross-linked fractal networks of several hundred nanometers. Transient absorption spectroscopy showed that BHJP facilitates polaron formation and electron transfer. Our BHJP demonstrated a superior hydrogen evolution rate (HER) compared to traditional methods. The most active BHJP achieved an HER of 251.2 mmol h–1 g–1 and an apparent quantum yield of 26.2% at 500 nm. This work not only introduces a practical method for preparing BHJP but also offers a new direction for the development of heterojunction materials.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"38 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Two Blatter Radicals Face-to-Face: A Constrained Diradical Architecture

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2024-12-20 DOI: 10.1021/jacs.4c16500

Paulina Bartos, Dominika Pomikło, Kadin B. Sorenson, Oleksandr Hietsoi, Andrienne C. Friedli, Piotr Kaszyński

引用次数: 0