ACS Central Science最新文献_第8页

Targeted Transcriptional Repression by Induced Proximity 通过诱导接近靶向转录抑制。

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-07-22 Epub Date: 2026-06-11 DOI: 10.1021/acscentsci.5c02277

Christian E. Stieger, Xinru Chen, Christina C. Kuismi, Dustin Dovala, Daniel Fuller, Andreas O. Frank, Mikias Woldegiorgis, Megan Bruce-Smythe, Fabian Wu, Nicolas Pizzato, Jeffrey McKenna, Cory Johannessen, Barna D. Fodor, Markus Schirle and Daniel K. Nomura*,

{"title":"Targeted Transcriptional Repression by Induced Proximity","authors":"Christian E. Stieger, Xinru Chen, Christina C. Kuismi, Dustin Dovala, Daniel Fuller, Andreas O. Frank, Mikias Woldegiorgis, Megan Bruce-Smythe, Fabian Wu, Nicolas Pizzato, Jeffrey McKenna, Cory Johannessen, Barna D. Fodor, Markus Schirle and Daniel K. Nomura*, ","doi":"10.1021/acscentsci.5c02277","DOIUrl":"10.1021/acscentsci.5c02277","url":null,"abstract":"Many transcription factors are considered “undruggable”and challenging targets due to the absence of ligandable pockets,large swaths of intrinsically disordered regions, and rapid turnover.Here, we describe a new induced-proximity therapeutic modality, Transcriptional Repression via Active Chemical Epigenetic Reprogramming (TRACER), that enforces locus-specific transcriptionalsilencing by recruiting endogenous corepressor complexes to transcriptionfactor binding sites. We developed small-molecule TRACERs that tethermethyl-CpG binding domain protein 2 (MBD2), a component of the NucleosomeRemodeling and Deacetylase (NuRD) complex, to transcription factor-directedligands. Recruitment of the NuRD complex by an estrogen receptor (ER)TRACER potently suppressed ER transcriptional activity in breast cancercells, downregulated ER target genes, and required MBD2 and histonedeacetylase (HDAC1/2) for activity, confirming on-target epigeneticrepression. Extending this approach to prostate cancer, an androgenreceptor (AR) TRACER transcriptionally repressed both full-lengthAR and the drug-resistant truncation variant, AR-V7, thereby achieving>90% inhibition of AR-dependent transcription in androgen-independentprostate cancer cells with locus-specific gene repression. Collectively,these findings establish TRACERs as a generalizable modality to pharmacologicallysilence transcription factors through targeted epigenetic reprogramming,offering a powerful strategy for treating cancers refractory to existingtherapies.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 7","pages":"1008–1020"},"PeriodicalIF":11.1,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583057","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

Synthesis Based on Covalent Capture and Release Enables Purification-free Fluorogenic Probe Libraries for Single-Molecule Protease Activity Profiling 基于共价捕获和释放的合成使纯化无荧光探针文库用于单分子蛋白酶活性分析。

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-07-22 Epub Date: 2026-06-29 DOI: 10.1021/acscentsci.6c00783

Mayano Minoda, Tadahaya Mizuno, Takumi Iwasaka, Hiroyuki Kusuhara, Yu Kagami, Shingo Sakamoto, Norimichi Nagano, Chiaki Hori, Kazufumi Honda, Yasuteru Urano and Toru Komatsu*,

{"title":"Synthesis Based on Covalent Capture and Release Enables Purification-free Fluorogenic Probe Libraries for Single-Molecule Protease Activity Profiling","authors":"Mayano Minoda, Tadahaya Mizuno, Takumi Iwasaka, Hiroyuki Kusuhara, Yu Kagami, Shingo Sakamoto, Norimichi Nagano, Chiaki Hori, Kazufumi Honda, Yasuteru Urano and Toru Komatsu*, ","doi":"10.1021/acscentsci.6c00783","DOIUrl":"10.1021/acscentsci.6c00783","url":null,"abstract":"Direct measurement of enzyme activities provides functionalinsightsinto complex biological systems; however, their broader applicationis limited by the lack of scalable strategies to generate diverse,assay-ready fluorogenic probes. In particular, conventional probesynthesis relies on chromatographic purification, preventing the rapidand parallel exploration of substrate space at the library scale.Here, we report synthesis based on covalent capture and release (SCCR),a general chemical strategy that enables purification-free generationof fluorogenic probe libraries. By embedding a covalent capture handlewithin a removable protecting group, SCCR establishes a standardizedcapture–elongation–release workflow that decouples moleculardiversification from chromatographic purification while retainingthe flexibility of liquid-phase synthesis. This approach enables automatedpreparation of high-purity probe libraries compatible with sensitiveactivity assays. Using this platform, we generated a library of over100 fluorogenic probes and applied it to profile protease activitiesat the single-molecule level, enabling substrate discovery and theactivity-based identification of disease-associated enzymatic signaturesin blood samples. These results establish a scalable route to functionalprobe generation and expand the accessible space for single-moleculeenzyme activity profiling in complex biological systems.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 7","pages":"1048–1056"},"PeriodicalIF":11.1,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583098","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

Polymer-Coated Nanoarchitectonics of Titanium Dioxide Nanoparticles with Enhanced Antimicrobial Activity: Mechanistic Insights into Localized Particle–Membrane Interactions 具有增强抗菌活性的二氧化钛纳米颗粒的聚合物包被纳米结构：局部颗粒-膜相互作用的机制见解。

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-07-22 Epub Date: 2026-06-18 DOI: 10.1021/acscentsci.6c00511

Nizar B. Alsharif*, Lucrezia Caselli, Anders Thapper, Emma Sparr and Martin Malmsten,

{"title":"Polymer-Coated Nanoarchitectonics of Titanium Dioxide Nanoparticles with Enhanced Antimicrobial Activity: Mechanistic Insights into Localized Particle–Membrane Interactions","authors":"Nizar B. Alsharif*, Lucrezia Caselli, Anders Thapper, Emma Sparr and Martin Malmsten, ","doi":"10.1021/acscentsci.6c00511","DOIUrl":"10.1021/acscentsci.6c00511","url":null,"abstract":"While surface modifications are widely pursued to improveantimicrobialperformance of photocatalytic nanoparticles (NPs), the particle–membraneinteractions responsible for these effects remain underexplored. Weaddress this gap by investigating the influence of coating TiO2 NPs with the cationic polymer poly(2-(dimethylamino)ethylmethacrylate) methyl chloride quaternary salt (qPDMAEMA). In contrastto bare TiO2, the coated NPs adsorb extensively to negativelycharged bacteria and bacteria-like membranes, boosting membrane permeabilizationupon UV illumination due to formation of reactive oxygen species (ROS).The qPDMAEMA coating was demonstrated not to interfere with ROS formationand to withstand UV illumination over time-scales sufficient for membranebinding and disruption. Such effects were highly localized near membrane-boundNPs, consistent with the short diffusion lengths of ROS (≈10nm for hydroxyl radicals) and the formation of oxidative membrane‘hot-spots’ in the corresponding vicinity of membraneregions where preferential (localized) NP binding occurs. Such preferentiallocalization is demonstrated to occur at poles and nodes of Escherichia coli bacteria. Hypothesizing this to be drivenby colocalization with anionic cardiolipin, studies with giant vesiclescontaining cardiolipin either uniformly distributed or present insegregated domains showed that the polymer-coated TiO2 NPspreferentially bind to cardiolipin-rich regions of the membrane. Together,these results expand on conventional studies of NP interactions withbacteria and bacteria-like membranes and demonstrate that localizedinteractions must be considered in studies of bacterial membrane interactionsof photocatalytic NPs.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 7","pages":"951–964"},"PeriodicalIF":11.1,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583112","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

When Organic Meets Solid: A Crystal-Clear Path to Better Batteries 当有机与固体相遇：通往更好电池的清晰之路

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-06-24 Epub Date: 2026-06-09 DOI: 10.1021/acscentsci.6c00932

Xiaodong Lin, and , Alexandru Vlad,

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These Graphene Experts Are Trying to Close the Reproducibility Gap in Two-Dimensional Materials Research 这些石墨烯专家正试图缩小二维材料研究的可重复性差距

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-06-24 Epub Date: 2026-05-13 DOI: 10.1021/acscentsci.6c00777

Mark Peplow,

引用次数: 0

Optimizing Antiseizure Candidate Compounds Using Deuterium Substitution 利用氘取代优化抗癫痫候选化合物

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-06-24 Epub Date: 2026-06-12 DOI: 10.1021/acscentsci.6c00941

Amy Cheng, and , Renae M. Ryan*,

引用次数: 0

Correction to “Hazardous Chemicals Pile Up in K–12 Science Laboratories” 更正“K-12科学实验室危险化学品堆积”

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-06-24 Epub Date: 2026-05-29 DOI: 10.1021/acscentsci.6c00816

Myriam Vidal Valero,

引用次数: 0

Small Organic Molecule-Based Multicolor Fluorescent Smart Materials: From Design Principles and Optical Properties to Versatile Applications 基于小有机分子的多色荧光智能材料：从设计原理和光学特性到多功能应用

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-06-24 Epub Date: 2026-05-18 DOI: 10.1021/acscentsci.6c00693

Zhen Yan, Taihong Liu*, Liping Ding* and Yu Fang,

{"title":"Small Organic Molecule-Based Multicolor Fluorescent Smart Materials: From Design Principles and Optical Properties to Versatile Applications","authors":"Zhen Yan, Taihong Liu*, Liping Ding* and Yu Fang, ","doi":"10.1021/acscentsci.6c00693","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00693","url":null,"abstract":"As an emerging frontier in functional material science, multicolor fluorescent smart materials have garnered significant interest because of their inherent versatility and precisely tunable fluorescent characteristics, enabling the development of increasingly sophisticated and functional platforms. In this Outlook, we summarize the recent advances in small-organic-molecule-based multicolor fluorescent materials, covering their design principles, optical properties, and versatile applications. The various strategies for achieving multicolor fluorescence emission could range from classic approaches based on modulation of electronic excited states and molecular intrinsic structure to newly emerging methods, such as molecular conformation switching and regulation of molecular aggregation/packing. We also present the advanced applications of the multicolor fluorescent materials driven by these design strategies, including fluorescence sensing, anticounterfeiting, information encryption, and decryption. Finally, an outlook on the main challenges and future opportunities for multicolor fluorescent materials is previewed, aiming to accelerate the advancement of smart materials and devices. We hope that these insights will inspire further innovative research on multicolor fluorescent smart materials and their advanced applications.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"751–765"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00693","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299734","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

Capacitively Coupled Alternating Electric Field for Accelerated and General Synthesis of Metal–Organic Frameworks 电容耦合交变电场用于金属-有机骨架的加速和一般合成

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-06-24 Epub Date: 2026-05-12 DOI: 10.1021/acscentsci.6c00250

Chaoting Shi, Yu Wang, Zhuolin Jin, Yilin Liu, Rongxin Yuan, Haibo Jiang, Yan Zhou* and Bing Xia*,

{"title":"Capacitively Coupled Alternating Electric Field for Accelerated and General Synthesis of Metal–Organic Frameworks","authors":"Chaoting Shi, Yu Wang, Zhuolin Jin, Yilin Liu, Rongxin Yuan, Haibo Jiang, Yan Zhou* and Bing Xia*, ","doi":"10.1021/acscentsci.6c00250","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00250","url":null,"abstract":"The conventional synthesis of metal–organic frameworks (MOFs) is often time-consuming and energy-intensive, which has become a bottleneck restricting their practical applications. Herein, we report a novel strategy utilizing a capacitively coupled alternating electric field (CCAEF) to accelerate MOF synthesis. The CCAEF could activate the precursor solution and lower the nucleation energy barrier, thereby facilitating the rapid formation of MOF materials. Using UiO-66 as a model, rapid synthesis was achieved within 25 min under relatively mild conditions, and the obtained material exhibited crystallinity and stability comparable to those of products from traditional synthesis methods. Furthermore, this method demonstrated good generality, successfully applied to the synthesis of various zirconium-based MOFs (e.g., UiO-66-NH2, MOF-801, MOF-808) and nonzirconium-based MOFs (e.g., MOF-5, MIL-88A, MIL-53). Notably, the CCAEF enhanced electron transfer, promoting the reduction of multivalent metals and leading to superior catalytic activity. This study provides an efficient strategy for the rapid and efficient synthesis of MOFs.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"831–840"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299722","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

How to Make a Creamy, Tasty Vegan Camembert 如何制作奶油味、美味的素食卡门培尔奶酪

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-06-24 Epub Date: 2026-05-26 DOI: 10.1021/acscentsci.6c00840

Marta Zaraska,

引用次数: 0