Analytical Chemistry最新文献

{"title":"Ultrasensitive and Specific Detection of Neutralization-Correlated Serum Antibodies Via Secondary Antibody−DNA Linker-Mediated Magnetic Bead−Based Proximity Extension Assay","authors":"Long Zhao,&nbsp;Yujue Wang,&nbsp;Lin Xiao,&nbsp;Shiyu Cao,&nbsp;Wei Wang,&nbsp;Feng Ye","doi":"10.1021/acs.analchem.6c03485","DOIUrl":"10.1021/acs.analchem.6c03485","url":null,"abstract":"<p>Sensitive, accurate, and readily deployable detection of neutralizing antibody (NAb) titers is essential for evaluating vaccine efficacy and population-level immunity. Here, we report an Antibody-DNA Linker (AND Linker) comprising a fusion of Protein A/G, a G4S flexible peptide, and duck circovirus replication initiator protein (DCV). This design enables orthogonal, site-specific assembly: the N-terminal Protein A/G binds the IgG Fc region, while the C-terminal DCV covalently captures 5′ ssDNA at a defined 1:1 molar ratio. Unlike random chemical crosslinking, which suffers from heterogeneous attachment sites, variable stoichiometry, and poor reproducibility, the AND Linker ensures uniform functional orientation and minimal batch-to-batch variation. By optimizing ssDNA secondary structure, we further enhanced DCV recognition efficiency. Integrating this linker into a magnetic bead-based proximity extension assay (termed SADL-MPEA), we achieved femtomolar-level detection of serum antibodies highly correlated with neutralizing activity. For HPV16 and HPV18, SADL-MPEA demonstrated limits of detection (LOD) approximately three orders of magnitude lower than conventional PEA using random chemical conjugation. In clinical serum validation against the pseudovirus neutralization test (PBNT), SADL-MPEA showed strong concordance (Pearson’s <em>r</em> = 0.84−0.85), confirming its utility as a reliable surrogate for functional neutralization capacity. Diagnostic performance was exceptional, with sensitivities of 90.9% (HPV16) and 83.3% (HPV18), 100% specificity for both, and an area under the ROC curve of 0.99. Crucially, SADL-MPEA requires only antigen-coated magnetic beads to adapt to new targets, as the DNA-labeled secondary antibody remains universal. This platform offers a simple, high-throughput, and scalable solution for NAb-correlated antibody detection in research and clinical settings.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 44","pages":"30480–30491"},"PeriodicalIF":7.3,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209445","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}

{"title":"A Multiple Signal Amplification Strategy from the Cascade Reactions of Catalytic Hairpin Assembly and Hybridization Chain Reaction for a Novel Bioelectronic Sensor","authors":"Junyong Lou,&nbsp;Jiajun Zhan,&nbsp;Futing Wang,&nbsp;Yujin Li,&nbsp;Yifan Lyu,&nbsp;Hongfen Yang,&nbsp;Dan Yang,&nbsp;Ren Cai,&nbsp;Weihong Tan","doi":"10.1021/acs.analchem.6c03093","DOIUrl":"10.1021/acs.analchem.6c03093","url":null,"abstract":"<p>A highly sensitive bioelectronic sensor (BES) was developed to analyze miRNA-182, utilizing Ag@Au hexagonal nanoplates (Ag@Au HNPs) in conjunction with catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) cascade reactions. The Ag@Au HNPs improve the conductivity between glucose oxidase (GOD) and carbon paper (CP), thereby contributing to enhanced electron transport in the BES. In addition, the multi-amplification strategy of the BES integrates the CHA-HCR cascade reaction with a capacitor to efficiently amplify the detection signal and enhance the sensitivity. As a result, the BES enables highly sensitive detection of miRNA-182 with a low limit of detection (LOD) of 0.34 fM (S/N = 3) in a wide linear response range of 1∼10⁴ fM. Furthermore, the BES exhibited significant applicability in the detection of miRNA-182 in real samples.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 44","pages":"30318–30326"},"PeriodicalIF":7.3,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209448","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}

{"title":"High-Performance 19F-Tags in Detecting Protein “Hot Spots” in Live Mammalian Cells","authors":"Chao-Yu Cui,&nbsp;Xia-Yan Li,&nbsp;Mo-Han Li,&nbsp;Yu-Hao Xiao,&nbsp;Xun-Cheng Su","doi":"10.1021/acs.analchem.6c02561","DOIUrl":"10.1021/acs.analchem.6c02561","url":null,"abstract":"<p>The understanding of weak protein interactions in native intracellular environments remains challenging due to macromolecular crowding, transient associations, and the highly heterogeneous chemical and spatial landscape of live cells. In-cell ¹⁹F NMR has been shown to be a promising tool for the characterization of intracellular interactions and dynamics of proteins, but the quality and sensitivity of ¹⁹F-reporters in detecting intracellular protein interactions remain largely unexplored. Here, we systematically designed and synthesized ten ¹⁹F-tags (<strong>T1</strong>−<strong>T10</strong>) with diverse hydrophobicity and rigidity. The ¹⁹F-tag was site-specifically installed in ubiquitin via thiol conjugation chemistry. We then examined the protein−¹⁹F-tag conjugates across various crowding media including chemical reagents, proteins, and cell lysates. Our findings reveal that the chemical structure of ¹⁹F-tags is critical for accurately reflecting the intrinsic behavior of the target protein. Unexpectedly, certain ¹⁹F-tags themselves, despite their small sizes, tend to interact transiently with commonly used crowding media (such as BSA), thereby confounding authentic protein interactions. Crucially, the live-cell NMR assay demonstrated that the ¹⁹F-tag <strong>T8</strong> (3-chloro-2-(phenylsulfonyl)-5-(trifluoromethyl)pyridine) (PSPy-m3F), featuring a shorter linker tether and a balanced amphiphilic profile, serves as an optimal ¹⁹F NMR reporter. It effectively resolves ubiquitin “hot spots” that are highly sensitive to weak intracellular interactions, providing a useful high-resolution tool for in-cell structural biology.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 44","pages":"30247–30255"},"PeriodicalIF":7.3,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209449","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}

{"title":"Isotope-Coded Click Chemistry-Enabled Enrichment for Reliable Profiling and Quantification of Carboxyl Metabolites","authors":"Xin Tao,&nbsp;Min Ren,&nbsp;Tao Zhang,&nbsp;Hou-Kai Li,&nbsp;Jian-Bo Wan","doi":"10.1021/acs.analchem.6c05924","DOIUrl":"10.1021/acs.analchem.6c05924","url":null,"abstract":"<p>Carboxyl-containing metabolites are involved in diverse biological processes and are closely associated with metabolic diseases. However, their sensitive and reliable profiling by liquid chromatography−mass spectrometry (LC−MS) remains challenging because of low endogenous abundance, inefficient electrospray ionization, and substantial interference from complex biological matrices. Here, we developed a click chemistry-enabled enrichment (CCEE) strategy that integrates isotope-coded derivatization with chemoselective enrichment for sensitive and selective profiling and quantification of carboxyl-containing metabolites in biological samples. CCEE markedly improved detection sensitivity and chromatographic performance while effectively reducing matrix interference. The method also exhibited good linearity, reproducibility, and quantitative accuracy. Application of CCEE to human serum enabled broad profiling of the carboxyl submetabolome and revealed metabolic alterations associated with metabolic dysfunction-associated fatty liver disease (MAFLD). Targeted absolute quantification of representative metabolites further validated the observed alterations. Notably, serum bilirubin levels were significantly lower in individuals with MAFLD and strongly correlated with multiple clinical indicators. Overall, CCEE provides a sensitive and selective strategy for profiling and quantifying the carboxyl submetabolome, facilitating the investigation of metabolic dysregulation and the discovery of candidate biomarkers for metabolic diseases.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 44","pages":"31846–31854"},"PeriodicalIF":7.3,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209453","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}

{"title":"When Two Interfaces Meet: A Unified Theory for Thin-Membrane Voltammetric Ion Selective Electrodes","authors":"Javier López-Asanza,&nbsp;Edward Zamudio,&nbsp;Angela Molina,&nbsp;Gastón A. Crespo,&nbsp;María Cuartero,&nbsp;Eduardo Laborda","doi":"10.1021/acs.analchem.6c03127","DOIUrl":"10.1021/acs.analchem.6c03127","url":null,"abstract":"<p>Voltammetric solid-contact ion-selective electrodes (SC-ISEs) exhibit electrochemical responses that arise from the coupling of heterogeneous electron transfer at the electrode−membrane interface with ion transfer at the membrane−sample boundary. In this work, a novel theoretical framework is developed for voltammetric SC-ISEs based on thin membranes, capturing the intrinsic consequences of coupling two polarized interfaces in series under markedly different mass-transport conditions in the membrane and solution phases. The theory describes the current/charge−potential−time responses and the corresponding interfacial potentials and dynamic ion and redox-species concentrations, accounting for the effects of membrane and solution composition, membrane thickness, and experimental timescale. Besides, the theory enables quantitative analysis of experimental voltammetric outcomes. A systematic classification of cyclic voltammetry (CV) responses is obtained in terms of three dimensionless parameters that quantify ion availability in the sample solution relative to the confined membrane. Simple relationships for peak positions and practical diagnostic criteria based on CV shape and scan-rate dependence are derived to verify thin-membrane conditions and the absence of kinetic or ohmic limitations, identifying indeed whether charge compensation proceeds via ion release or uptake.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 44","pages":"30348–30358"},"PeriodicalIF":7.3,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209963","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}

{"title":"Synergistic Integration of Water-Stable 2D Perovskite Heterojunctions and Self-Priming DNA Walkers for Sensitive Photoelectrochemical Biosensing","authors":"Chaomin Gao,&nbsp;Haihan Yu,&nbsp;Shenguang Ge,&nbsp;Jinghua Yu","doi":"10.1021/acs.analchem.6c05016","DOIUrl":"10.1021/acs.analchem.6c05016","url":null,"abstract":"<p>Two-dimensional Ruddlesden−Popper (2D RP) perovskites hold immense promise as light-harvesting photoactive materials for photoelectrochemical (PEC) bioanalysis, yet their poor aqueous durability and suboptimal charge-carrier dynamics severely restrict PEC sensing implementation. Herein, we report a dual-functional strategy that simultaneously addresses both challenges through the in-situ construction of a Z-scheme heterojunction, (BA)₂PbI₄−Pb(OH)₂ (BA = butylammonium), via Lewis base vapor diffusion. The Pb(OH)₂ barrier formed during synthesis acts as a robust protective shield that preserves the perovskite’s structural integrity, while the intimate Z-scheme heterointerface constructed in the heterojunction remains functional and continues to accelerate spatial charge separation even after three years of immersion in ultrapure water, as corroborated by electron paramagnetic resonance spectroscopy, photo-assisted Kelvin probe force microscopy, and density functional theory calculations. To further amplify the PEC signal, we engineer a circular DNA scaffold-supported tripedal DNA walker powered by self-priming polymerization, eliminating the requirement for exogenous primers in traditional polymerase-driven DNA nanomachines. Target-triggered autonomous walking of the tripedal DNA nanomachine continuously disassembles surface-tethered hairpin tracks, drastically mitigating interfacial steric hindrance and yielding prominent photocurrent enhancement. Synergizing the ultra-stable Z-scheme RP perovskite photoelectrode with the primer-free DNA walker, the integrated PEC sensing platform achieves ultrasensitive quantification of acetamiprid with a wide linear range spanning 10⁻¹³ to 10⁻⁶ M. This work establishes a new paradigm for rationally designing aqueous-stable perovskites and coupling them with intelligent molecular devices, paving the way for high-performance PEC sensing platforms.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 44","pages":"31328–31337"},"PeriodicalIF":7.3,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210006","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}

{"title":"Instrument-Agnostic Machine Learning Framework for Accurate Prediction of Functional Groups from Tandem Mass Spectrometry","authors":"Connor Beveridge,&nbsp;Prageeth R. Wijewardhane,&nbsp;Matthew Muhoberac,&nbsp;Nicolás M. Morato,&nbsp;Andreas Kaerner,&nbsp;Li-Kang Zhang,&nbsp;Douglas Richardson,&nbsp;Ayanna Shoulds,&nbsp;Jeffrey R. Gilbert,&nbsp;Christopher J. Welch,&nbsp;Shane Tichy,&nbsp;Gaurav Chopra","doi":"10.1021/acs.analchem.5c05945","DOIUrl":"10.1021/acs.analchem.5c05945","url":null,"abstract":"<p>Structural elucidation of unknown compounds using tandem mass spectrometry (MS/MS) is an ongoing challenge. Expert chemists will often use common product ion peaks and neutral losses or peak matching software to predict structural aspects from MS/MS spectra, a process which is time consuming and limited by the molecular entries in the database. We introduce an instrument-agnostic machine learning (ML) framework that predicts functional groups directly from MS/MS spectra, eliminating the need for conventional database searches. The ML models are trained on data from different sources, the MassBank of North America (MONA), a public database, and a custom MS/MS database acquired using a single high throughput desorption electrospray ionization (DESI) MS/MS platform to showcase transferability of model predictions independent of instrument acquisition. Additionally, a novel spectral representation is developed for ML use by standardizing the spectra to the precursor ion <em>m/z</em>. We utilized molecular metrics, specifically, average molecular F1 score of 87% (MONA) and 76% (DESI) and average molecular accuracy of 94% (MONA) and 87% (DESI), indicating similar model performance when trained on different databases to validate the ML framework. To further illustrate the robustness and transferability of our ML framework, models trained on DESI-generated data successfully predicted functional groups, using spectral data generated from a blind test set of molecules using two different company laboratories using distinct mass spectrometry instruments (Orbitrap and TOF) operated in positive-ion mode electrospray ionization. We believe that such an approach, where models trained on data from one instrument can reliably make accurate predictions on spectra acquired using different instruments in a database-free manner, will significantly expand the practical applications of ML to mass spectrometry.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 44","pages":"30122–30131"},"PeriodicalIF":7.3,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210136","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}

{"title":"Raspberry-Mimic Immunomagnetic Nanoparticles for Specific Capture of Neuronal-Enriched Extracellular Vesicles for Accurate Alzheimer’s Disease Diagnosis","authors":"Peijuan Xie,Haiyan Wang,Xuan Li,Hekai Zhang,Mingyuan Yin,Xueli Wang,Xiaoqiang Qiao","doi":"10.1021/acs.analchem.6c06296","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c06296","url":null,"abstract":"Alzheimer’s disease (AD) is an irreversible neurodegenerative disease, making noninvasive early diagnosis crucial for delaying disease progression and reducing the caregiving burden. Neuronal-enriched extracellular vesicles (NEEVs) have emerged as promising biomarkers for AD liquid biopsy. However, the scarcity of NEEVs and the lack of straightforward and specific enrichment methods limit their wider clinical application. Herein, we developed a novel capture strategy based on raspberry-mimic immunomagnetic nanoparticles (RIMNPs) for specific enrichment of intact NEEVs in one step. By combining analysis of dual NEEVs surface biomarkers NEEVs@p-tau217 and NEEVs@Aβ42 oligomers, a powerful model was constructed for accurate AD diagnosis. The RIMNPs ensure exceptionally specific enrichment of NEEVs while preserving their integrity and bioactivity. Compared with gold standard ultracentrifugation, the RIMNPs exhibited superior separation performance, achieving 5.9-fold enhancement in the purity of NEEVs. Furthermore, RIMNPs demonstrated efficient enrichment with 93.1% capture efficiency and 84.4% recovery. In clinical samples, the dual-biomarker combined with machine learning, yielding 96.4% sensitivity, 100% specificity and precision, and 98.2% accuracy in AD diagnosis, outperforming the discriminative performances of each single biomarker. This work integrates efficient enrichment of NEEVs by RIMNPs and detection of their surface dual-biomarkers, demonstrating superior diagnostic performance and offering a promising avenue for noninvasive, EVs-based liquid biopsy.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"9 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149374712","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}

{"title":"Computational Hapten Rationalization Unlocks Multiplex Lateral Flow Immunoassay for Quinolines","authors":"Jiaxun Li,Lingling Guo,Xinxin Xu,Liqiang Liu,Hua Kuang,Chuanlai Xu,Liguang Xu","doi":"10.1021/acs.analchem.6c05661","DOIUrl":"https://doi.org/10.1021/acs.analchem.6c05661","url":null,"abstract":"Computation-aided spacer-mismatch epitope engineering is implemented to generate highly specific monoclonal antibodies targeting two hazardous quinoline pollutants, hydroxyquinoline (HQL) and nitroxoline (NXO). These structurally similar quinoline derivatives are widely misused in agricultural and animal husbandry, bringing severe hidden risks to food and ecological environments. Molecular descriptors reflecting epitope exposure and skeleton integrity were adopted to screen optimal alkyl spacer lengths for rational hapten design. Combined with the hybridoma technology, two monoclonal antibodies with high affinity and specificity were successfully obtained. Half-maximal inhibitory concentrations determined by the indirect competitive enzyme-linked immunosorbent assay were 1.104 ng/mL and 1.671 ng/mL for HQL and NXO, respectively. Furthermore, a dual-color latex microsphere-based multiplex lateral flow immunoassay was developed for simultaneous detection of HQL and NXO in apple, chicken, and livestock wastewater. The proposed method achieved matrix-matched limits of detection of 5.898 μg/kg and 6.289 μg/kg in apple, 6.305 μg/kg and 7.279 μg/kg in chicken, and 2.450 μg/kg and 3.879 μg/kg in livestock wastewater for HQL and NXO, respectively. The method was validated via real sample analysis, demonstrating favorable accuracy and reliability, which was suitable for rapid and high-throughput on-site screening.","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"33 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149374713","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}

{"title":"IMSS: An Integrated Mass Spectrometry Strategy for Targeted Discovery of CyclopeptidesExemplified by Phakellicyclins from the Marine Sponge Phakellia fusca","authors":"Ying Wu,&nbsp;Jialan Yu,&nbsp;Ruyi Li,&nbsp;Jing Xu,&nbsp;Yun Zhang,&nbsp;Liyun Liu,&nbsp;Fan Sun,&nbsp;Houwen Lin,&nbsp;Shuping Wang","doi":"10.1021/acs.analchem.6c04128","DOIUrl":"10.1021/acs.analchem.6c04128","url":null,"abstract":"<p>Cyclopeptides (CPs) represent a structurally diverse class of bioactive natural products but remain analytically challenging due to their high structural similarity, low abundance, and complex matrices. Herein, we report an integrated mass spectrometry strategy (IMSS) enabling selective detection, annotation, and targeted isolation of CPs from marine organisms. The workflow incorporates: (1) multiplexed diagnostic neutral loss and precursor ion (NL/PI) scanning based on the six most frequent amino acid residues (Pro, Ile/Leu, Val, Tyr, Phe, Trp) identified from 16 reference standards; (2) de novo sequencing-assisted spectral validation via CycloNovo; (3) dual dereplication combining GNPS molecular networking with a curated library of 538 marine CPs; and (4) MS-triggered automated purification for target-oriented isolation. When applied to the marine sponge <em>Phakellia fusca</em>, IMSS afforded 23 candidate CPs and allowed targeted purification of two unknown cyclooctapeptides, phakellicyclins A and B, featuring rare dioxindolylalanine and β-3-oxindolylalanine residues, respectively. Both compounds exhibited potent anti-inflammatory activity through selective inhibition of interleukin-6 (IL-6) production without obvious cytotoxicity. This study establishes a robust and reproducible MS workflow for the targeted discovery of Pro/Ile/Leu-enriched marine CPs, with demonstrated potential for adaptation to other CP classes.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"98 44","pages":"30750–30763"},"PeriodicalIF":7.3,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149091907","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}