ACS Central Science最新文献_第8页

Targeting Sialidase to PD1 Enhances T cell Function and Tumor Control 唾液酸酶靶向PD1增强T细胞功能和肿瘤控制

IF 10.4 1区化学

ACS Central Science Pub Date : 2025-07-04 DOI: 10.1021/acscentsci.5c00510

Brett M. Garabedian, Eleanor E. Bashian, Xiaoshuang Wang, Andrew J. Thompson and James C. Paulson*,

{"title":"Targeting Sialidase to PD1 Enhances T cell Function and Tumor Control","authors":"Brett M. Garabedian, Eleanor E. Bashian, Xiaoshuang Wang, Andrew J. Thompson and James C. Paulson*, ","doi":"10.1021/acscentsci.5c00510","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00510","url":null,"abstract":"Immune therapies targeting the PD1 axis have transformed outcomes in cancer treatment by enhancing T cell-mediated immune responses. However, many tumors evade immune clearance through orthogonal escape mechanisms. Excessive production of immunosuppressive sialic acid-containing glycans (sialoglycans) can impair immune surveillance by recruiting inhibitory Siglecs to the immune synapse where, like PD1, they act as checkpoints for cell activation. Sialic acids can also impact T cell activation by dampening the ligation of the costimulatory receptor CD28 with its ligands. This polypharmacology implicates sialoglycans as a linchpin of tumor immunity that can be targeted to further improve outcomes of PD1 therapies. In this work we conjugated sialidase to anti-PD1 (αPD1-S) to selectively degrade sialic acids on immune cells expressing PD1. Glycan profiling confirmed targeted desialylation, and functional assays demonstrated enhancements to T cell activation and cytotoxic capacity. In a melanoma model, αPD1-S promoted inflammatory macrophage polarization and reduced T cell exhaustion, collectively restricting melanoma growth beyond anti-PD1 (αPD1) alone. By simultaneously blocking PD1 and degrading sialoglycans, αPD1-S provides a novel strategy to enhance T cell-mediated immune responses and improve tumor control in refractory cancers.Sialidase conjugated to anti-PD1 degrades inhibitory sialoglycans from PD1+ T cells and tumor cells, enhancing T cell activation and tumor control beyond PD1 blockade alone in refractory cancers.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 8","pages":"1417–1427"},"PeriodicalIF":10.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902058","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

Supramolecular Chiral Assembly Films with Dynamic Handedness and Emitting-Color Afterglow 具有动态手性和发光余辉的超分子手性组装膜。

IF 10.4 1区化学

ACS Central Science Pub Date : 2025-07-03 DOI: 10.1021/acscentsci.5c00847

Xinkun Ma, Wei Yuan, Wangjian Fang, Letian Chen, Zujin Zhao* and Yanli Zhao*,

{"title":"Supramolecular Chiral Assembly Films with Dynamic Handedness and Emitting-Color Afterglow","authors":"Xinkun Ma, Wei Yuan, Wangjian Fang, Letian Chen, Zujin Zhao* and Yanli Zhao*, ","doi":"10.1021/acscentsci.5c00847","DOIUrl":"10.1021/acscentsci.5c00847","url":null,"abstract":"This work presents a strategy for the fabrication of multicolor-emitting circularly polarized afterglow (CPA) films by assembling achiral phosphorescent donors and fluorescent emitters in a photonic crystal matrix. Achiral positively charged phosphors and fluorophores with good spectral overlap are selected as the donor and sequential receptors, which are then coassembled with poly(vinyl alcohol) and cellulose nanocrystals. CPA can be achieved in the blue to near-infrared (NIR) range with stepwise amplification of the dissymmetry factor (lifetime up to 4.52 s and dissymmetry factor up to −0.038) through synergistic chirality and energy transfer processes. Notably, the handedness of the CPA signal can be amplified or reversed by altering the receptor types or the direction of incident light. With the flexibility in manipulating emission and handedness, these materials show potential applications in multidimensional anticounterfeiting and high-definition noctilucent displays.Supramolecular assembly with chiral cellulose nanocrystal template and Förster resonance energy transfer cascade enables direction-switchable circularly polarized afterglow and NIR emission.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"1230–1239"},"PeriodicalIF":10.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725833","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

Is There More to Magic Mushrooms than Psilocybin? 除了裸盖菇素，还有什么神奇的蘑菇吗？

IF 10.4 1区化学

ACS Central Science Pub Date : 2025-07-03 DOI: 10.1021/acscentsci.5c01146

Mara Johnson-Groh,

引用次数: 0

Chemistries Moonshot: An Entirely Recyclable Car 化学领域的登月计划：一辆完全可回收的汽车。

IF 10.4 1区化学

ACS Central Science Pub Date : 2025-07-02 DOI: 10.1021/acscentsci.5c00589

Robin Schoemaker, Chunning Sun, Davide Chiarugi, Theodore Tyrikos-Ergas* and Peter H. Seeberger*,

{"title":"Chemistries Moonshot: An Entirely Recyclable Car","authors":"Robin Schoemaker, Chunning Sun, Davide Chiarugi, Theodore Tyrikos-Ergas* and Peter H. Seeberger*, ","doi":"10.1021/acscentsci.5c00589","DOIUrl":"10.1021/acscentsci.5c00589","url":null,"abstract":"Automobiles depend on fossil resources – both to create the device and to power it. The automotive industry has decreased this dependency on fossil fuels by developing more fuel-efficient combustion engines, lightweight designs, and biofuels. The rise of battery electric vehicles (BEVs) offers the chance to reduce the fossil footprint by avoiding fuel combustion and exhaust emission. Disruptive approaches toward a truly sustainable car are far from being market-ready. To reach a completely sustainable car, the automotive industry must address the carbon footprint of material production, which is based in the chemical sector. The automotive and chemical industries have to adopt closed-loop thinking, utilize renewable resources for biodegradables, as well as develop novel materials and designs for efficient recycling. Disruptive approaches can arise from predictive models that can accelerate chemical research and enable the discovery of sustainable materials with desirable recycling properties. Integrating generative artificial intelligence (AI) with high-throughput experimental validation will shorten material development cycles and advance the transition to more sustainable products. Moving toward a fully recyclable car is aligning research and development efforts from the chemical sector to the automotive industry and beyond, presenting a giant leap toward a circular economy.An outlook on sustainability in the auto industry, focusing on data-driven chemistry to reduce fossil dependency and enable a transition toward a circular economy.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"1052–1061"},"PeriodicalIF":10.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725799","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

Nanoparticles with Ampholytic Surfaces for Binding and Disintegration of Amyloid Fibrils 具有两性溶解表面的纳米颗粒用于淀粉样蛋白原纤维的结合和解体。

IF 10.4 1区化学

ACS Central Science Pub Date : 2025-07-02 DOI: 10.1021/acscentsci.5c00519

Suman Mandal, Minh Dang Nguyen, Nikhil Ranjan Jana* and T. Randall Lee*,

{"title":"Nanoparticles with Ampholytic Surfaces for Binding and Disintegration of Amyloid Fibrils","authors":"Suman Mandal, Minh Dang Nguyen, Nikhil Ranjan Jana* and T. Randall Lee*, ","doi":"10.1021/acscentsci.5c00519","DOIUrl":"10.1021/acscentsci.5c00519","url":null,"abstract":"Amyloid fibrils and associated protein aggregates are key contributors to a range of neurodegenerative diseases. Recent studies suggest that nanoparticles with tailored surface chemistries can effectively bind to and disrupt these fibrils. Here, we investigate the role of nanoparticle surface charge in mediating interactions with amyloid fibrils and promoting their disintegration. We synthesized seven types of charged iron oxide nanoparticles (cationic, anionic, and ampholytic) in colloidal form with hydrodynamic diameters ranging from 15 to 40 nm. Interaction studies with mature lysozyme fibrils revealed that ampholytic nanoparticles exhibited the highest binding affinity among the tested surface types. This enhanced affinity is attributed to reduced nonspecific interactions and favorable electrostatic compatibility. Ampholytic nanoparticles disrupted mature amyloid fibrils approximately 2.5 times more effectively than other surface-charged nanoparticles, leading to smaller fibril fragments via mechanical agitation. We further show that agitation-induced mechanical force, along with piezocatalytically generated reactive oxygen species (ROS), contributes to fibril degradation. These findings highlight the critical role of ampholytic surface charge in promoting fibril disintegration and suggest that such nanoparticles could be leveraged in therapeutic strategies for neurodegenerative diseases involving amyloid aggregation.Ampholytic nanoparticles bind and disintegrate amyloid fibrils efficiently via electrostatic interactions and ROS generation under agitation; cationic and anionic types are less effective.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"1218–1229"},"PeriodicalIF":10.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725826","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

Predictable C–H Functionalization of Complex beta-Fused Azines: A Mechanistically Bound Site-Specific Oxidation 可预测的C-H功能化络合物-融合Azines：机械结合位点特异性氧化。

IF 10.4 1区化学

ACS Central Science Pub Date : 2025-07-01 DOI: 10.1021/acscentsci.5c00797

Carla Obradors*, Christopher A. Reiher, Cristina Grosanu, Mikko Muuronen, Romain Tessier, Egor M. Larin and Valentin Lehuédé,

{"title":"Predictable C–H Functionalization of Complex beta-Fused Azines: A Mechanistically Bound Site-Specific Oxidation","authors":"Carla Obradors*, Christopher A. Reiher, Cristina Grosanu, Mikko Muuronen, Romain Tessier, Egor M. Larin and Valentin Lehuédé, ","doi":"10.1021/acscentsci.5c00797","DOIUrl":"10.1021/acscentsci.5c00797","url":null,"abstract":"Direct manipulation of C–H bonds enclosed in complex scaffolds persists today as an elusive disconnection when aiming for high and predictable site-selectivity. Its development toward the late-stage diversification of heterocycles remains of the upmost interest due to their ubiquitous presence in synthetic drugs and new methods consistently emerge to facilitate more versatile routes. The underlying challenge of activating a single C–H bond often leads to isomeric mixtures and a limited scope, which gets magnified in polycyclic frameworks, and the biased selectivity depending on the ring decoration recurrently hampers reliable retrosynthetic analyses. Here we report the straightforward C–H functionalization of multiple beta-fused azines toward a C–O bond formation with exclusive as well as predictable regiocontrol. Mild conditions enable the presence of a vast variety of motifs with orthogonal reactivity to transition-metals and highly sensitive moieties while also adding a divergent synthetic handle for further derivatizations in >10 distinct heterocyclic scaffolds.This work reports a facile C−H functionalization method for diverse fused azines with predictable site-selectivity that enables multiple synthetic derivatizations applicable for drug discovery.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"1189–1198"},"PeriodicalIF":10.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725828","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

Fast-Track Signaling: A Non-Adiabatic Photoactivation Pathway in Plant Cryptochromes 快速通道信号：植物隐色素的非绝热光激活途径。

IF 10.4 1区化学

ACS Central Science Pub Date : 2025-07-01 DOI: 10.1021/acscentsci.5c01100

Jorim M. Kornblueh, and , Ilia A. Solov’yov,

引用次数: 0

Design and Development of an Organocatalyst for Light Accelerated Amide and Peptide Synthesis 光加速酰胺和肽合成的有机催化剂的设计与开发。

IF 10.4 1区化学

ACS Central Science Pub Date : 2025-06-30 DOI: 10.1021/acscentsci.5c00487

Yiping Li, Jingyue Li, Zhouming Shen, Haoyu Kuang, Quan Zuo, Guangjun Bao, Jingman Ni, Wangsheng Sun* and Rui Wang,

{"title":"Design and Development of an Organocatalyst for Light Accelerated Amide and Peptide Synthesis","authors":"Yiping Li, Jingyue Li, Zhouming Shen, Haoyu Kuang, Quan Zuo, Guangjun Bao, Jingman Ni, Wangsheng Sun* and Rui Wang, ","doi":"10.1021/acscentsci.5c00487","DOIUrl":"10.1021/acscentsci.5c00487","url":null,"abstract":"The catalytic methods for amide and peptide synthesis have long been recognized as some of the most pressing challenges in industry and academia. Designing more attractive catalysts is crucial to addressing these challenges. Herein, we report a simple organocatalyst, named Cat-Se, for the direct synthesis of amides and peptides. The catalyst can simultaneously avoid many application barriers, thereby providing a good boost to applied research in the field. It can rapidly catalyze various carboxylic acids and amines to form amides in high yields under mild light irradiation conditions without any undesirable operations. The method exhibits high selectivity and maintains stereochemical integrity during peptide synthesis. Significantly, Cat-Se also shows effectiveness in peptide fragment condensation and solid-phase peptide synthesis, making it an attractive method for peptide drug synthesis.Cat-Se can catalyze amide/peptide synthesis under mild light. It shows high yield, stereoselectivity, and compatibility with SPPS, advancing sustainable catalytic methods for peptide drug synthesis.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"1240–1249"},"PeriodicalIF":10.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725818","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

High-Yield Prebiotic Polymerization of 2′,3′-Cyclic Nucleotides under Wet–Dry Cycling 干湿循环条件下2 ',3 ' -环核苷酸的高产聚合

IF 10.4 1区化学

ACS Central Science Pub Date : 2025-06-28 DOI: 10.1021/acscentsci.5c00488

Federico Caimi, , , Juliette Langlais, , , Francesco Fontana, , , Sreekar Wunnava, , , Tommaso Bellini*, , , Dieter Braun*, , and , Tommaso P. Fraccia*,

{"title":"High-Yield Prebiotic Polymerization of 2′,3′-Cyclic Nucleotides under Wet–Dry Cycling","authors":"Federico Caimi, , , Juliette Langlais, , , Francesco Fontana, , , Sreekar Wunnava, , , Tommaso Bellini*, , , Dieter Braun*, , and , Tommaso P. Fraccia*, ","doi":"10.1021/acscentsci.5c00488","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00488","url":null,"abstract":"The spontaneous formation of RNA polymers is a fundamental yet challenging step for the origin of life. Here we show that 2′,3′-cyclic nucleotides of all four nucleobases efficiently polymerize without external activators when subjected to wet–dry cycling at room temperature in a mild alkaline pH range. We found conditions where oligomerization yields (Y) are enhanced by wet–dry cycling, reaching Y ≈ 70% for guanosine and Y ≥ 20% for other nucleobases. Microscopy monitoring during the drying process indicates that guanosine’s higher reactivity stems from its self-assembly propensity at pH ≤ 10. At pH 11, guanosine ordering is disfavored, leading to a nearly stoichiometrically balanced polymerization of the four nucleotides with Y = 36%. Only water is added at each cycle, mimicking humid nights and dry days on early Earth. This leads to a broad distribution of A, U, G, and C mixed sequence oligomers, up to 6% of 4-mer and 0.1% of 10-mer, paving the way for RNA replication and evolution through subsequent templated ligation under the same pH. The combination of simple boundary conditions and a pathway toward RNA evolution makes this process a compelling model for the prebiotic origin of RNA on early Earth.Wet−dry cycles at mild alkaline pH drive high-yield spontaneous RNA polymerization from 2′,3′-cyclic nucleotides without added molecules, offering a simple route for RNA formation on early Earth.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1546–1557"},"PeriodicalIF":10.4,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117245","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

The Assembly of a High-Efficiency Tris-benzotriazolate-Based Metal–Organic Framework Solid-State Electrolyte 高效三苯并三唑酸盐基金属-有机框架固态电解质的组装。

IF 10.4 1区化学

ACS Central Science Pub Date : 2025-06-27 DOI: 10.1021/acscentsci.5c00567

Zhangyi Xiong, Shitao Wu, Liang Gu, Mengyang Zhai, Yuke Pan, Yanhang Ma* and Zhijie Chen*,

{"title":"The Assembly of a High-Efficiency Tris-benzotriazolate-Based Metal–Organic Framework Solid-State Electrolyte","authors":"Zhangyi Xiong, Shitao Wu, Liang Gu, Mengyang Zhai, Yuke Pan, Yanhang Ma* and Zhijie Chen*, ","doi":"10.1021/acscentsci.5c00567","DOIUrl":"10.1021/acscentsci.5c00567","url":null,"abstract":"Metal–organic frameworks (MOFs) with tunable ion transport pathways are considered promising solid-state electrolyte (SSE) candidates for developing lithium or sodium metal batteries. However, their low ionic conductivity and inferior stability with metal anodes limit practical applications. Herein we synthesized a high-stability tris-benzotriazolate-based MOF─Cu-TTBT─with ordered pore channels for SSE applications via a network-directed approach. Cu-TTBT, overcoming the synthetic challenge of tritopic benzotriazolate-based linkers, greatly advances the field of azolate-based MOFs. The resultant framework displays fast ion transport pathways with a high ionic conductivity of 1.83 × 10–4 S cm–1 and 1.1 × 10–4 S cm–1 at 298 K for Cu-TTBT-Li and Cu-TTBT-Na, respectively, among the highest in azolate-based MOFs. The Li|SSE|LiFePO4 and Na|SSE|Na3V2(PO4)3 coin cells exhibit stable cycling performances over 200 cycles at 1.0 C and 298 K. This research advances the synthetic chemistry of azolate-based MOFs and paves the way for the development of robust frameworks with high-efficiency SSE performances.We rationally synthesized a tris-benzotriazolate-based MOF with high ionic conductivities, offering a synthetic chemistry approach to the development of next-generation energy storage systems.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"1199–1206"},"PeriodicalIF":10.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725834","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