ACS Central Science最新文献

{"title":"Selective and Potent Peptide Binders of RNF43 for Wnt Signaling Inhibition","authors":"Sunhee Hwang,&nbsp;, ,&nbsp;Paula Flórez Salcedo,&nbsp;, ,&nbsp;Antonion Korcari,&nbsp;, ,&nbsp;John M. Nicoludis,&nbsp;, ,&nbsp;Estefania Martinez Valdivia,&nbsp;, ,&nbsp;Lingling Peng,&nbsp;, ,&nbsp;Aaron T. Balana,&nbsp;, ,&nbsp;Justin Mak,&nbsp;, ,&nbsp;Christopher M. Crittenden,&nbsp;, ,&nbsp;Amin Famili,&nbsp;, ,&nbsp;Peter Liu,&nbsp;, ,&nbsp;David Castillo-Azofeifa,&nbsp;, ,&nbsp;Rami N. Hannoush,&nbsp;, ,&nbsp;Stephen E. Miller,&nbsp;, ,&nbsp;Christina I. Schroeder,&nbsp;, and ,&nbsp;Xinxin Gao*,&nbsp;","doi":"10.1021/acscentsci.5c00744","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00744","url":null,"abstract":"<p >The Wnt/β-catenin pathway is critical in human tumor progression. Cell-surface transmembrane E3 ubiquitin ligase ring finger 43 negatively regulates Wnt signaling through ubiquitination of Wnt coreceptor Frizzled. Aberrant Wnt signaling through inactivating mutations of RNF43 has been identified in various forms of cancers, highlighting its significance in tumor biology. However, the precise mechanism underlying the function of RNF43 remains elusive, largely due to the absence of selective molecular tools allowing for detection or manipulation of endogenous RNF43. Here we present a series of disulfide-constrained peptides, including GUR-1.6.12.2, which exhibit high affinity and specificity against RNF43. GUR-1.6.12.2 can be used as a valuable research tool to delineate RNF43 activity in various contexts. We showcased its application in immunofluorescence, where RNF43 was detected in intestinal crypts using biotinylated GUR-1.6.12.2. We then combined experimental and computational structural approaches to propose a model of GUR-1.6.12.2 and its binding to RNF43. Importantly, we generated a functional RNF43-DCP by producing a hexavalent GUR-1.6.12.2 molecule, which exhibited inhibitory activity against Wnt signaling in cells by competing with R-spondin, a RNF43 ligand that potentiates signaling. The RNF43 binders presented here offer new opportunities for the research and development of anticancer therapies targeting Wnt signaling with improved selectivity.</p><p >Here we report the development of selective and potent disulfide-constrained peptide binders of RNF43. The functional hexavalent peptide inhibits Wnt signaling in cells by competing with R-spondin.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1670–1681"},"PeriodicalIF":10.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00744","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117257","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}

{"title":"Illuminating Mitochondrial Dynamics: Ultrahigh Labeling Stability Probe for Long-Term SIM Super-Resolution Imaging of Mitochondria","authors":"Xiangpeng Lin,&nbsp;, ,&nbsp;Xuelei Pang,&nbsp;, ,&nbsp;Yue Huang,&nbsp;, ,&nbsp;Xinxin Duan,&nbsp;, ,&nbsp;Yunfei Wei,&nbsp;, ,&nbsp;Ning Jing,&nbsp;, ,&nbsp;Meng Zhang*,&nbsp;, and ,&nbsp;Yu-Hui Zhang*,&nbsp;","doi":"10.1021/acscentsci.5c00695","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00695","url":null,"abstract":"<p >Delineating intricate mitochondrial dynamic changes over extended time scales through combined fluorescent probes and super-resolution microscopy is pivotal for deciphering the pathogenesis of mitochondrial-related diseases. However, a major challenge lies in the scarcity of probes that simultaneously exhibit robust labeling stability, exceptional photostability, and minimal cytotoxicity. Herein, rational design and screening yielded a novel covalent mitochondrial probe, HZ Mito Red. Due to its exceptional covalent labeling efficiency, HZ Mito Red exhibits superior mitochondrial labeling stability, with a 10-fold improvement compared to Mito Tracker Red (MTR). Furthermore, it exhibits remarkable photostability, retaining over 80% fluorescence after 300 SIM images, and negligible phototoxicity, preserving mitochondrial integrity even after 400 SIM images of continuous imaging. These advantageous properties facilitated the pioneering of high signal-to-noise, long-term dynamic SIM super-resolution imaging of mitochondria during ferroptosis, apoptosis, and autophagy, achieving unprecedented detailed delineation of mitochondrial morphology. Additionally, engineered for multichannel mitochondrial imaging, HZ Mito Deep Red mirrors the exceptional labeling stability of HZ Mito Red, achieving near-phototoxicity-free dynamic tracking with 60% fluorescence retention after 300 SIM images. Significantly, both HZ Mito Red and HZ Mito Deep Red are compatible with cell immunofluorescence staining. This study provides a robust and versatile tool for the in-depth analysis of mitochondrial dynamics in disease states.</p><p >Novel covalent mitochondrial fluorescent probes with excellent labeling stability, high photostability, and low phototoxicity allow long-term SIM super-resolution dynamic imaging of mitochondria.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1700–1714"},"PeriodicalIF":10.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00695","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117256","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}

{"title":"Data-Driven Prediction of Enantioselectivity for the Sharpless Asymmetric Dihydroxylation: Model Development and Experimental Validation","authors":"Blake E. Ocampo,&nbsp;, ,&nbsp;Bilal Altundas,&nbsp;, ,&nbsp;Matthew J. Bock,&nbsp;, ,&nbsp;Sara Feiz,&nbsp;, and ,&nbsp;Scott E. Denmark*,&nbsp;","doi":"10.1021/acscentsci.5c00900","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00900","url":null,"abstract":"<p >The Sharpless asymmetric dihydroxylation remains a key transformation in chemical synthesis, yet its success hides unexpected cases of lower selectivity. A chemoinformatic workflow was developed to allow data-driven analysis of the reaction. A database of 1007 reactions employing AD-mix α and β was curated from the literature, and an alignment-dependent, fragment-based featurization of alkenes was implemented for modeling. This platform converged on machine learning models capable of predicting the magnitude of enantioselectivity for multiple alkene classes, achieving <i>Q</i>²_F3 values ≥ 0.8, test <i>r</i>² values ≥ 0.7 and mean absolute errors (MAE) ≤ 0.3 kcal/mol. The features of alkenes contributing to model performance were assessed with SHapley Additive exPlanations (SHAP) analysis to gather insight into factors underlying predictions. Experimental validation demonstrated that the models could achieve meaningful predictions on out-of-sample alkenes.</p><p >A data-driven approach was designed to analyze the Sharpless Asymmetric Dihydroxylation for insight into factors driving enantioselectivity and high-performing models were experimentally validated</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1640–1650"},"PeriodicalIF":10.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00900","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117305","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}

{"title":"Recruitment of Aβ into α-Synuclein Condensates Catalyzes Primary Nucleation of α-Synuclein Aggregation","authors":"Owen M. Morris,&nbsp;Alexander Röntgen,&nbsp;Zenon Toprakcioglu*,&nbsp;Mariana Cali,&nbsp;Samuel Dada and Michele Vendruscolo*,&nbsp;","doi":"10.1021/acscentsci.5c00614","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00614","url":null,"abstract":"<p >The aggregation of amyloid-β (Aβ) and α-synuclein (αSyn) is linked to Alzheimer’s and Parkinson’s diseases, with growing evidence suggesting possible interactions between Aβ and αSyn in the pathology of these neurodegenerative conditions. In this context, the recent observation that protein aggregation into amyloid fibrils may take place within liquid condensates generated through liquid–liquid phase separation prompts the question of how amyloidogenic proteins interact with each other, and more specifically whether Aβ can influence the overall phase behavior of αSyn or vice versa. To address this question, we investigated the interplay between Aβ40, the most abundant form of Aβ, with αSyn. We found that monomeric Aβ40 is sequestered into αSyn condensates, where it enhances heterogeneous primary nucleation, and accelerates the aggregation of αSyn within the liquid condensates. Using a chemical kinetics framework, we further showed that this liquid-to-solid transition is not significantly affected by adding preformed Aβ40 fibrillar seeds, further indicating that monomeric Aβ40 specifically enhances the primary nucleation of αSyn within the condensed phase. These findings identify some of the key mechanistic processes underlying amyloid aggregation within liquid condensates, prompting further investigations into the possible role of Aβ and αSyn cocondensation interactions in the onset and progression of neurodegenerative disorders.</p><p >This study reports the effect of amyloid-β (Aβ) on the phase transitions of α-synuclein (αSyn), showing that Aβ40 is recruited into αSyn condensates where it accelerates αSyn amyloid aggregation.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 8","pages":"1481–1491"},"PeriodicalIF":10.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902053","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}

{"title":"Mesoporous Potassium-Based Metal–Organic Framework as a Drug Carrier","authors":"Bo Fang,&nbsp;, ,&nbsp;Tianyu Shan,&nbsp;, ,&nbsp;Sailing Chen,&nbsp;, ,&nbsp;Fei Pan,&nbsp;, ,&nbsp;Xue Yang,&nbsp;, ,&nbsp;Ding Xiao,&nbsp;, ,&nbsp;Feihe Huang*,&nbsp;, and ,&nbsp;Zhengwei Mao*,&nbsp;","doi":"10.1021/acscentsci.5c00904","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00904","url":null,"abstract":"<p >To date, the number of reported mesoporous metal–organic frameworks (MOFs) remains limited. Herein, we report a novel mesoporous potassium-based MOF (K-MOF), designated as <b>KMOF-1</b>, whose precise structure was determined by using single-crystal X-ray diffraction. <b>KMOF-1</b> used 18-crown-6 units as the organic linkers and potassium ions as the metal centers, forming a framework topological structure with interconnected four-membered rings. The specific surface area of the synthesized <b>KMOF-1</b> was determined by the Brunauer–Emmett–Teller method, which showed a high specific surface area of 1034 m²/g. <b>KMOF-1</b> was demonstrated to be a promising drug carrier, exhibiting encapsulation capabilities for various drugs and maintaining stability for a defined period under simulated physiological conditions. Using vascular endothelial growth factor (VEGF) aptamers as model drugs, we further confirmed the effective loading of VEGF aptamers in <b>KMOF-1</b> (<b>KMOF-1@VEGF</b>) and the ability of <b>KMOF-1@VEGF</b> to release VEGF aptamers responsively in acidic environments. Additionally, in vitro studies showed that <b>KMOF-1</b> protected VEGF aptamers from degradation by nucleases, allowing them to be effectively taken up by cells. This novel K-MOF, with its biocompatible metal centers, mesoporous channels, and demonstrated efficacy as a drug carrier, offers a significant advancement in developing MOF-based drug delivery systems.</p><p >The mesoporous structure, high drug loading capacity, and biocompatibility of <b>KMOF-1</b> make it a promising candidate for biomedical applications.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1651–1658"},"PeriodicalIF":10.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117303","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}

{"title":"","authors":"Carla Obradors*,&nbsp;Christopher A. Reiher,&nbsp;Cristina Grosanu,&nbsp;Mikko Muuronen,&nbsp;Romain Tessier,&nbsp;Egor M. Larin and Valentin Lehuédé,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678347","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}

{"title":"","authors":"Gustavo J. Costa,&nbsp; and ,&nbsp;Ruibin Liang*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678348","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}

{"title":"","authors":"Jennifer K. Bailey,&nbsp;Satoru Horiya,&nbsp;Mahesh Neralkar,&nbsp;Viktor Horvath,&nbsp;Kosuke Nakamoto,&nbsp;J. Sebastian Temme,&nbsp;Raphael J. Turra and Isaac J. Krauss*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00539","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678373","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}

{"title":"","authors":"Yibin Sun,&nbsp;Yue Fang,&nbsp;Yajie Liu,&nbsp;Fengyi Jiang,&nbsp;Zhichao Lei,&nbsp;Hanyu Gao* and Wen-Bin Zhang*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678374","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}

{"title":"","authors":"Xinkun Ma,&nbsp;Wei Yuan,&nbsp;Wangjian Fang,&nbsp;Letian Chen,&nbsp;Zujin Zhao* and Yanli Zhao*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":12.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678381","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}