ACS Chemical Biology最新文献_第10页

Tau-Targeted PROTACs Degrade Pathology-Associated Tau and Improve Memory in Alzheimer’s Disease Models Tau靶向PROTACs在阿尔茨海默病模型中降低病理相关Tau并改善记忆

IF 3.6 2区生物学

ACS Chemical Biology Pub Date : 2026-08-21 Epub Date: 2026-07-28 DOI: 10.1021/acschembio.6c00096

Tian Zhao, Tian-Yang Wang, Hao-Sen Wang, Yeh-Jun Lim, Zhi-Jun Zhang, Xin-Rong Duan, Liang Li, Yan-Mei Li

{"title":"Tau-Targeted PROTACs Degrade Pathology-Associated Tau and Improve Memory in Alzheimer’s Disease Models","authors":"Tian Zhao, Tian-Yang Wang, Hao-Sen Wang, Yeh-Jun Lim, Zhi-Jun Zhang, Xin-Rong Duan, Liang Li, Yan-Mei Li","doi":"10.1021/acschembio.6c00096","DOIUrl":"https://doi.org/10.1021/acschembio.6c00096","url":null,"abstract":"Tau aggregation and hyperphosphorylation are key pathologicalfeaturesof Alzheimer’s disease (AD). Because Tau is intrinsically disordered,conventional small-molecule inhibitors have achieved limited success.Proteolysis-targeting chimeras (PROTACs) enable the targeted proteasomaldegradation of previously considered undruggable proteins. We designedTau-targeted PROTAC candidates using methylene blue (MB) as a recognitionmoiety for aggregation-prone motifs within the microtubule-bindingregion and varied the linker lengths and E3 ligase recruitment ligandsto optimize degradation efficiency. Cell-based screening revealedthat MB-2-VHL1 and MB-2-VHL2 are active degraders. In vivo studiesconfirmed a reduction in total Tau levels and degradation of phosphorylatedTau (p-Tau). In 3xTg-AD mice, subcutaneous administration of MB-2-VHL2was associated with reduced hippocampal Tau and p-Tau levels and improvedrecognition memory and spatial learning. MB-2-VHL2 was also detectablein both serum and brain tissue by LC–MS/MS after subcutaneousadministration and did not cause detectable histological or biochemicaltoxicity. These results indicate that MB-2-VHL2 can reduce both totalTau and p-Tau levels in vivo. Although the reduction in p-Tau appearedmore pronounced under our experimental conditions, whether MB-2-VHL2preferentially targets pathological Tau remains to be determined.Overall, these findings support further optimization and preclinicalevaluation of Tau-targeted PROTACs as a potential therapeutic strategyfor AD.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"21 8","pages":"1906–1916"},"PeriodicalIF":3.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fragment-Based Discovery of Fenamic Acids as Pan-Species Inhibitors of the Soluble Epoxide Hydrolase Phosphatase Domain 基于片段的芬胺酸作为可溶性环氧化物水解酶磷酸酶结构域泛物种抑制剂的发现

IF 3.6 2区生物学

ACS Chemical Biology Pub Date : 2026-08-21 Epub Date: 2026-07-28 DOI: 10.1021/acschembio.6c00502

W. Felix Zhu, Guillaume Feugray, Steffen Brunst, Hind Messaoudi, Meng Yang, Noemi Martinez-Conde, Andreas Krämer, Lilia Weizel, Johanna M. H. Ehrler, Jan S. Kramer, Astrid Kaiser, Mohammad Al-Tarrass, Tony Pereira, Manon Valet, Valéry Brunel, Manfred Schubert-Zsilavecz, Stefan Knapp, Felix F. Lillich, Victor Hernandez-Olmos, Thomas Duflot, Kerstin Hiesinger, Hongwu Qian, Anna Proschak, Jeremy Bellien, Ewgenij Proschak

{"title":"Fragment-Based Discovery of Fenamic Acids as Pan-Species Inhibitors of the Soluble Epoxide Hydrolase Phosphatase Domain","authors":"W. Felix Zhu, Guillaume Feugray, Steffen Brunst, Hind Messaoudi, Meng Yang, Noemi Martinez-Conde, Andreas Krämer, Lilia Weizel, Johanna M. H. Ehrler, Jan S. Kramer, Astrid Kaiser, Mohammad Al-Tarrass, Tony Pereira, Manon Valet, Valéry Brunel, Manfred Schubert-Zsilavecz, Stefan Knapp, Felix F. Lillich, Victor Hernandez-Olmos, Thomas Duflot, Kerstin Hiesinger, Hongwu Qian, Anna Proschak, Jeremy Bellien, Ewgenij Proschak","doi":"10.1021/acschembio.6c00502","DOIUrl":"https://doi.org/10.1021/acschembio.6c00502","url":null,"abstract":"Targeting the N-terminal phosphatase domain of solubleepoxidehydrolase (sEH) could potentially represent a pharmacological strategyfor treatment of cardiometabolic diseases. However, development ofchemical tools to investigate the therapeutic potential of sEH phosphatase(sEH-P) inhibition has proven challenging due to varying activitiesbetween different species isoforms and lack of selectivity towardthe C-terminal hydrolase domain, which exhibits the epoxide hydrolaseactivity (sEH-H). Herein, we describe the fragment-based discoveryof FZ581 (49), an sEH-P inhibitor against human, rat,and mouse isoforms. In vivo studies with this compound in mice andrats demonstrated a significant increase of main sEH-P substrate levelswithout affecting plasma levels of sEH-H substrates. Altogether, weprovide a pan-species sEH-P inhibitor to study the pharmacotherapeuticpotential of sEH-P inhibition.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"21 8","pages":"2053–2067"},"PeriodicalIF":3.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defining Glycan Recognition by DC-SIGN Using Native Mass Spectrometry 用天然质谱法定义DC-SIGN聚糖识别。

IF 3.6 2区生物学

ACS Chemical Biology Pub Date : 2026-08-21 Epub Date: 2026-07-25 DOI: 10.1021/acschembio.6c00397

Duong T. Bui, Elena N. Kitova, Lara K. Mahal, John S. Klassen

{"title":"Defining Glycan Recognition by DC-SIGN Using Native Mass Spectrometry","authors":"Duong T. Bui, Elena N. Kitova, Lara K. Mahal, John S. Klassen","doi":"10.1021/acschembio.6c00397","DOIUrl":"10.1021/acschembio.6c00397","url":null,"abstract":"C-type lectins (CTLs), many of whichbind carbohydrates(glycans)in a Ca2+-dependent manner, are an important family ofglycan-binding proteins that play essential roles in immune recognitionand regulation. Among them, dendritic cell–specific ICAM-3-grabbingnonintegrin (DC-SIGN) is notable for its ability to recognize a broadrange of self- and pathogen-derived glycans. Despite extensive study,the glycan binding specificity of DC-SIGN remains incompletely understood,in part because accurately quantifying intrinsic lectin–glycanbinding affinities across diverse glycan repertoires remains challenging.Here, we employ native mass spectrometry (nMS), a label- and immobilization-freeapproach well suited for probing weak lectin–glycan interactions,to characterize the glycan-binding preferences of the carbohydraterecognition domain (CRD) of DC-SIGN. Native MS, applied directly orvia a catch-and-release (CaR) strategy, enabled quantitative measurementsand high-throughput screening under physiologically relevant, nonvolatilesalt conditions. We further examined the binding of several divalentmetal ions to the DC-SIGN CRD and their influence on glycan recognition.Although divalent cations other than Ca2+ bind the CRDwith comparable affinity, they exert only modest effects on ligandbinding. Screening a defined glycan library, including oligomannoses,human milk oligosaccharides, Lewis and blood group antigens, and gangliosideoligosaccharides, revealed a preference for oligomannoses and Lewisantigens, with affinity positively correlated with the number of mannoseor fucose residues. Finally, application of CaR-nMS to a natural N-glycan library identified fucosylated N-glycans as DC-SIGN ligands. Together, these results define the glycanspecificity of DC-SIGN and establish nMS as a platform for comprehensiveinteractome profiling of CTLs.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"21 8","pages":"1980–1990"},"PeriodicalIF":3.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Craspase Protease Activation Is Sensitive to Oncogenic Single-Nucleotide RNA Mismatches 葡萄蛋白酶活化对致癌单核苷酸RNA错配敏感。

IF 3.6 2区生物学

ACS Chemical Biology Pub Date : 2026-08-21 Epub Date: 2026-07-15 DOI: 10.1021/acschembio.6c00241

Dani Feldmann, Sam P. B. van Beljouw, Anna C. Haagsma, Konstantinos Kalogeropoulos, Aswin Muralidharan, Stan J. J. Brouns

{"title":"Craspase Protease Activation Is Sensitive to Oncogenic Single-Nucleotide RNA Mismatches","authors":"Dani Feldmann, Sam P. B. van Beljouw, Anna C. Haagsma, Konstantinos Kalogeropoulos, Aswin Muralidharan, Stan J. J. Brouns","doi":"10.1021/acschembio.6c00241","DOIUrl":"10.1021/acschembio.6c00241","url":null,"abstract":"The type III-E CRISPR-controlled protease Craspase isdistinguishedfrom other type III systems by its single-subunit RNA-guided proteincomplex and direct coupling of RNA recognition to protease activationwithout second messenger signaling, making it an attractive developmentplatform for bioengineering and therapeutics. Here, we identify fivepositions within the CRISPR RNA (crRNA) of Craspase from Candidatus “Scalindua brodae” (Sb-Craspase)that are sensitive to single-nucleotide mismatches. We leverage thesepositions to design crRNAs that selectively target clinically relevantsingle-nucleotide variants (SNVs) in oncogenic RNA transcripts. Usingthis approach, Sb-Craspase is selectively activatedby the “undruggable” KRAS G12D SNV,while the wild-type transcript does not induce protease activation.Collectively, our results establish a framework for designing crRNAsto target clinically relevant SNVs, laying the groundwork for Craspase-baseddiagnostics and therapeutics against otherwise intractable oncogenicmutations.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"21 8","pages":"1877–1882"},"PeriodicalIF":3.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transition Metal Activation Reframes SAMHD1 Regulation 过渡金属活化重构SAMHD1调控。

IF 3.6 2区生物学

ACS Chemical Biology Pub Date : 2026-08-21 Epub Date: 2026-07-15 DOI: 10.1021/acschembio.6c00438

Logan A. Calderone, Anthony Gizzi, Soumika Pinninti, James T. Stivers, Maria-Eirini Pandelia

{"title":"Transition Metal Activation Reframes SAMHD1 Regulation","authors":"Logan A. Calderone, Anthony Gizzi, Soumika Pinninti, James T. Stivers, Maria-Eirini Pandelia","doi":"10.1021/acschembio.6c00438","DOIUrl":"10.1021/acschembio.6c00438","url":null,"abstract":"SAMHD1 is the lonehuman dNTP triphosphohydrolase andis linkedto antiviral defense, nucleotide pool homeostasis, chemotherapy resistance,and the autoinflammatory Aicardi-Goutières syndrome. Althoughits substrate specificity and nucleotide-dependent oligomerizationhave been extensively studied, the identity and mechanistic rolesof its metal cofactors remain poorly understood. Here, we integrateselective metal enrichment, spectroscopy, biochemical reconstitution,and enzyme kinetics to define the metal requirements underlying SAMHD1activation and catalysis. We show that robust SAMHD1 activity is preferentiallysupported by transition metals and that the enzyme readily assemblesmultiple iron-containing dinuclear active sites in solution. Ironpreferentially binds to one position of the bimetallic core and promotesrecruitment of a second divalent metal required for catalysis. Althoughmanganese can substitute for iron, it alters metal-binding equilibriaand less efficiently supports dinuclear cofactor assembly, highlightinga specialized organizational role for iron. In contrast, the secondsite remains comparatively permissive and accommodates various divalentmetal ions with distinct functional consequences. Mixed-metal activesites further retain catalytic activity across redox conditions thatotherwise suppress activity in homodinuclear diiron configurations,suggesting that metal plasticity buffers SAMHD1 against oxidativeinhibition. Transition metals additionally act as higher-affinityallosteric activators than Mg2+, revealing that metal identitycontributes to both catalytic and regulatory layers of SAMHD1 function.Cumulatively, these findings redefine the metal requirements of SAMHD1and establish a framework in which iron-dependent active site organizationand mixed-metal flexibility cooperate to sustain dNTP hydrolysis underchanging cellular environments and metal flux conditions.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"21 8","pages":"2001–2011"},"PeriodicalIF":3.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Determinants of Ribosome Binding for the Antimicrobial Peptide Pdi1 抗菌肽Pdi1核糖体结合的分子决定因素。

IF 3.6 2区生物学

ACS Chemical Biology Pub Date : 2026-08-21 Epub Date: 2026-07-23 DOI: 10.1021/acschembio.6c00052

Trevor T. Dean, Alyah Ziyad, Dorota Klepacki, José A. Villegas, Terry W. Moore

{"title":"Molecular Determinants of Ribosome Binding for the Antimicrobial Peptide Pdi1","authors":"Trevor T. Dean, Alyah Ziyad, Dorota Klepacki, José A. Villegas, Terry W. Moore","doi":"10.1021/acschembio.6c00052","DOIUrl":"10.1021/acschembio.6c00052","url":null,"abstract":"Type II proline-richantimicrobial peptides have emergedas promisingtherapeutic candidates due to their ability to inhibit a previouslyundrugged stage of bacterial protein synthesis: translation termination.The recent characterization of the potent Type II proline-rich antimicrobialpeptide, Pdi1, suggests that it may represent a promisingtherapeutic candidate; however, no information is available concerningits ribosome-binding activity. The lack of biochemical and biophysicalassays to interrogate the binding affinities and mechanism of actionof this class of peptides presents a bottleneck in the drug-discoverypipeline. In this study, we report the first characterization of theribosome-binding kinetics of a Type II proline-rich antimicrobialpeptide, for which we applied a biolayer interferometry assay to studythe Pdi1–ribosome interaction. Our results revealslow dissociation kinetics, which indicates prolonged residence timein the ribosomal nascent peptide exit tunnel. Additionally, alaninescanning of the Pdi1 C-terminus revealed that specificresidues are critical for ribosome binding and contribute to the rateof Pdi1 dissociation. These findings were validated incell-based assays where alanine substitutions at these positions reducedantibiotic activity. We also demonstrated that a Pdi1 derivative, which lacks the third-to-last pharmacophoric residue,fails to inhibit translation termination, despite retaining a submicromolarminimum inhibitory concentration. These results demonstrate that selectresidues in the Pdi1 pharmacophore play a critical rolein ribosome binding and dissociation, in addition to inhibiting translationtermination.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"21 8","pages":"1897–1905"},"PeriodicalIF":3.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biotin Ligase-Based Reporter for Detecting Protease Activity 基于生物素连接酶的蛋白酶活性检测报告基因。

IF 3.6 2区生物学

ACS Chemical Biology Pub Date : 2026-08-21 Epub Date: 2026-07-22 DOI: 10.1021/acschembio.6c00334

Jennifer Sescil, Isabel Solowiej, Guanwei Zhou, Tae Heo, Emma Fu, Wenjing Wang

引用次数: 0

Synthesis and Characterization of Radio-Halogenated Talazoparib Analogues for Imaging and Radioligand Therapy 用于成像和放射配位治疗的放射性卤代塔拉唑帕尼类似物的合成和表征。

IF 3.6 2区生物学

ACS Chemical Biology Pub Date : 2026-08-21 Epub Date: 2026-07-27 DOI: 10.1021/acschembio.6c00253

Riccardo Muzzioli, Federica Pisaneschi, Seth T. Gammon, Margie N. Sutton, Arianna Napoli, Raffaele Bellini Puglielli, Lauren McIntosh, Evgeny Tereshatov, Gabriel Tabacaru, Steven Schultz, Laura McCann, Jonathan D. Burns, Sherry Yennello, David Piwnica-Worms

{"title":"Synthesis and Characterization of Radio-Halogenated Talazoparib Analogues for Imaging and Radioligand Therapy","authors":"Riccardo Muzzioli, Federica Pisaneschi, Seth T. Gammon, Margie N. Sutton, Arianna Napoli, Raffaele Bellini Puglielli, Lauren McIntosh, Evgeny Tereshatov, Gabriel Tabacaru, Steven Schultz, Laura McCann, Jonathan D. Burns, Sherry Yennello, David Piwnica-Worms","doi":"10.1021/acschembio.6c00253","DOIUrl":"10.1021/acschembio.6c00253","url":null,"abstract":"Talazoparib (TZ) is a potent poly(ADP-ribose) polymerase1/2 (PARP1/2)inhibitor that uniquely traps PARP complexes at sites of single-strandDNA damage thereby offering opportunities for targeted radioligandtherapy. Radiolabeled halogenated TZ derivatives were synthesizedusing boronic ester precursors to enable incorporation of diagnosticand therapeutic radionuclides: 18F for PET imaging, 77Br for Auger electron radiotherapy, and 211Atfor targeted alpha radiotherapy. Copper-mediated radio-halogenationafforded racemic 18F-TZ, 77Br-TZ, and 211At-TZ in sufficient radiochemical yields (4.3 ± 2.6%, n = 33; 29.0 ± 12.0%, n = 4; 3.6 ±3.8%, n = 9, respectively), ∼99% radiochemicalpurity and proven stability under formulation conditions. Moleculardynamics simulations of halo-TZ derivatives predicted an inverse relationshipbetween halogen size and PARP1 binding affinity. Indeed, cell uptakeof radio-halogenated TZ analogues indicated selective uptake in apanel of cell types that correlated with PARP1 levels but was inverselyrelated to the atomic radii of the halogen series. Despite modestspecific activity and specific uptake, 77Br-TZ showed significantcytotoxicity. Further investigation of 18F-TZ with 77Br-TZ as a radiotheranostic pair will be facilitated by thesynthetic schemes herein.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"21 8","pages":"1883–1890"},"PeriodicalIF":3.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical Interactions between the Common Soil Bacteria Pseudomonas chlororaphis and Bacillus subtilis 土壤常见细菌绿假单胞菌与枯草芽孢杆菌的化学相互作用。

IF 3.6 2区生物学

ACS Chemical Biology Pub Date : 2026-08-21 Epub Date: 2026-07-20 DOI: 10.1021/acschembio.6c00420

Zohar Tik, Shaked Uzi-Gavrilov, Bat-El Hagbi-Lazar, David C. Nwobodo, Orit Sivan, Michael M. Meijler

{"title":"Chemical Interactions between the Common Soil Bacteria Pseudomonas chlororaphis and Bacillus subtilis","authors":"Zohar Tik, Shaked Uzi-Gavrilov, Bat-El Hagbi-Lazar, David C. Nwobodo, Orit Sivan, Michael M. Meijler","doi":"10.1021/acschembio.6c00420","DOIUrl":"10.1021/acschembio.6c00420","url":null,"abstract":"Chemical signaling between soil inhabitants is of tremendousimportanceto the health of many ecosystems, and at the same time detailed molecularknowledge underlying these conversations is surprisingly scarce. Oneof the major bacterial genera inhabiting the rhizosphere is Pseudomonas, of which most species are known to producephenazines, which carry antibiotic properties. Pseudomonas chlororaphis, a common rhizosphere dwelling specieswith plant growth-promoting traits, produces phenazine-1-carboxamide(PCN). This study examines how the production of PCN by Pseudomonas affects another common species in soilthat it often encounters, namely Bacillus subtilis. When both species were cultured at close distance, distinct andvisible changes in colony morphologies were observed without changesin growth rates. Interestingly, a clear transformation occurred inthe morphology of B. subtilis coloniesin the presence of supplemented PCN, indicating the role of phenazinesin affecting colony morphology. In addition, untargeted metabolomicsanalyses showed a decrease in the production of plipastatin and surfactinby B. subtilis in the presence of P. chlororaphis. Our results indicate that PCN induceschanges in morphology and signaling of B. subtilis without significantly affecting its growth. We hypothesize that P. chlororaphis and B. subtilis sense one another and act to conserve energy while avoiding competition.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"21 8","pages":"1991–2000"},"PeriodicalIF":3.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efforts Toward XNA PCR: Optimization and Characterization of PCR-Amplification of Chimeric 2′F XNA/DNA 向XNA PCR的努力：优化和鉴定嵌合2'F XNA/DNA的PCR扩增

IF 3.6 2区生物学

ACS Chemical Biology Pub Date : 2026-08-21 Epub Date: 2026-07-27 DOI: 10.1021/acschembio.6c00270

Helen V. Branson, Aria A. Khalique, Mia J. Kronson, Delaney I. Carlin, Avery E. Roof, Madison K.C. Seto, Ysabel David, Michelle Cao, Susanna E. Barrett, Taiasean Wu, Aaron M. Leconte

{"title":"Efforts Toward XNA PCR: Optimization and Characterization of PCR-Amplification of Chimeric 2′F XNA/DNA","authors":"Helen V. Branson, Aria A. Khalique, Mia J. Kronson, Delaney I. Carlin, Avery E. Roof, Madison K.C. Seto, Ysabel David, Michelle Cao, Susanna E. Barrett, Taiasean Wu, Aaron M. Leconte","doi":"10.1021/acschembio.6c00270","DOIUrl":"https://doi.org/10.1021/acschembio.6c00270","url":null,"abstract":"Xeno Nucleic Acids(XNA) are chemically modified versions of DNA.These modifications can bypass natural immune responses and impartnovel properties in complex biological systems. Previous efforts haveidentified mutant proteins capable of robust XNA synthesis; one mutant,SFM4-3, has been shown to be able to amplify partially substitutedXNA in the polymerase chain reaction (PCR) which is necessary formany applications of XNA. However, SFM4-3 mediated PCR is inefficientand has required up to 22 h of reaction time to create amplicons of∼75 nucleotides (nt); optimizing the PCR amplification of XNAcan potentially improve its utility. Here, we show an optimized methodfor XNA PCR and compare the XNA PCR ability of mutant XNA polymeraseenzymes. We show that SFP1 and SFP4 perform better than SFM4-3 inthe amplification of 2′F-XNA. We also highlight the role ofprotein stability in XNA polymerase PCR performance, demonstratingthat significantly diminished thermostability may limit current XNApolymerases. This work decreases the time needed for XNA PCR to <4h, increases the length of amplicons generated to 245 nt, identifiesnew PCR-active enzymes, and provides guidance for how to improve XNApolymerases for PCR in the future.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"21 8","pages":"1927–1936"},"PeriodicalIF":3.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0