Journal of the American Society for Mass Spectrometry最新文献

Proteoform Characterization of HIV-1 Broadly Neutralizing Antibody PGT 121.414.LS Product Through Middle-Up and Bottom-Up Proteomics for Clinical Support. HIV-1广泛中和抗体PGT 121.414的蛋白形态特征LS产品通过中向上和自下而上的蛋白质组学进行临床支持。

IF 2.7 2区化学

Journal of the American Society for Mass Spectrometry Pub Date : 2025-10-02 DOI: 10.1021/jasms.5c00198

Connor E Gould, Qing Ma, Raymond Cha, Valerie A Frerichs, Alan E Friedman, Robin DiFrancesco, Gene D Morse, Troy D Wood

{"title":"Proteoform Characterization of HIV-1 Broadly Neutralizing Antibody PGT 121.414.LS Product Through Middle-Up and Bottom-Up Proteomics for Clinical Support.","authors":"Connor E Gould, Qing Ma, Raymond Cha, Valerie A Frerichs, Alan E Friedman, Robin DiFrancesco, Gene D Morse, Troy D Wood","doi":"10.1021/jasms.5c00198","DOIUrl":"https://doi.org/10.1021/jasms.5c00198","url":null,"abstract":"Broadly neutralizing antibody (bNAb) therapies are under development for the prevention and treatment of HIV-1 infection as an alternative to conventional antiretroviral therapy because of their potential for sustained passive immunotherapy. Currently, bNAbs targeting the HIV-1 viral envelope proteins are included in research protocols to evaluate their role in preventing transmission and in combination antiviral regimens to achieve viral suppression. While quantification of bNAbs is of clinical importance, validation of the structural fidelity of therapeutic antibodies is also an important consideration to assess the clinical efficacy. Here, we applied middle-up and bottom-up proteomics workflows for the quality assurance of the primary structure of the HIV-1 bNAb PGT 121.414.LS product. Middle-up and bottom-up proteomics workflows were performed using liquid chromatography coupled to an Orbitrap mass spectrometer. Middle-up analysis of the crystallizable fragment (Fc/2), light chain (Lc), and fragment denaturation (Fd, N-terminal fragment of the heavy chain) regions of PGT 121.414.LS was performed by using IdeS digestion, which revealed proteoform heterogeneity. To complement the middle-up approach, a bottom-up workflow combining trypsin and chymotrypsin digests was performed for detailed glycoform mapping and annotation. The bottom-up results indicated that Lc contained an additional N-terminal Ser residue. For the Fc, two abundant and two lower-abundance glycoforms of the heavy chain were detected that correspond to Asn-312 (Asn-297 in the consensus heavy chain sequence of IgG). For Fd, bottom-up analysis revealed eight sialylated glycoforms and five nonsialylated glycoforms at Asn-124 of the heavy chain. The results emphasize bNAb heterogeneity, which should be considered in affinity binding studies.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

ASMS from an Editor-in-Chief's Perspective: Welcoming an Industrial Associate Editor to the JASMS Team. 从总编辑的角度看asm：欢迎行业副编辑加入JASMS团队。

IF 2.7 2区化学

Journal of the American Society for Mass Spectrometry Pub Date : 2025-10-02 DOI: 10.1021/jasms.5c00291

Jenny Brodbelt

引用次数: 0

Improving the Quadrupole to Ion Mobility Region in a Digital Quadrupole/Ion Mobility/Orbitrap Mass Spectrometer. 改进数字四极杆/离子迁移率/轨道阱质谱仪的四极-离子迁移区。

IF 2.7 2区化学

Journal of the American Society for Mass Spectrometry Pub Date : 2025-10-02 DOI: 10.1021/jasms.5c00142

Robert L Schrader, Gordon A Anderson, Kacie A Evans, David H Russell

{"title":"Improving the Quadrupole to Ion Mobility Region in a Digital Quadrupole/Ion Mobility/Orbitrap Mass Spectrometer.","authors":"Robert L Schrader, Gordon A Anderson, Kacie A Evans, David H Russell","doi":"10.1021/jasms.5c00142","DOIUrl":"https://doi.org/10.1021/jasms.5c00142","url":null,"abstract":"A quadrupole/drift tube ion mobility/Orbitrap instrument requires pumping from atmosphere to 10-5 Torr in the quadrupole analyzer region, back to 1 Torr for the drift tube, and a return to 10-5 Torr for the Orbitrap high vacuum region. The Orbitrap high vacuum region contains the transfer multipole, C-trap, and HCD cell. Insufficient pumping between the drift tube and quadrupole leads to helium in the quadrupole analyzer chamber which compromises performance. Additional vacuum regions were added between the drift tube and the analyzer chamber to maintain the analyzer pressure below 5.5 × 10-5 Torr with the drift tube pressurized to 1.5 Torr of He. In this configuration, the isolation of a single charge state of C-reactive protein (m/z 5,000) was demonstrated. Fourier transform ion mobility spectra were acquired with the quadrupole in full scan mode and in the isolation mode. Ion optic voltages were optimized for both helium and nitrogen bath gases in the drift tube so that minimal ion heating was observed entering the drift tube. These instrument modifications enable improved ion transfer efficiency, allowing for better ion isolation by the digital quadrupole ion mobility separation of large protein complexes, as illustrated by the 23+ and 24+ charge states of C-reactive protein.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

An Integrated Strategy for Rapid Profiling of Depsipeptides by High-Performance Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry: Bombyx batryticatus as an Example. 高效液相色谱-四极杆飞行时间质谱联用快速分析沉积肽的综合策略：以瓢虫为例。

IF 2.7 2区化学

Journal of the American Society for Mass Spectrometry Pub Date : 2025-10-02 DOI: 10.1021/jasms.5c00259

Huijie Sun, Yang Li, Yunhua Feng, Kaicheng Xie, Jinyi Sui, Ting Wu, Hongliang Zhou, Guoliang Dai, Chengyao Ma, Jiandong Zou, Meijuan Xu

{"title":"An Integrated Strategy for Rapid Profiling of Depsipeptides by High-Performance Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry: Bombyx batryticatus as an Example.","authors":"Huijie Sun, Yang Li, Yunhua Feng, Kaicheng Xie, Jinyi Sui, Ting Wu, Hongliang Zhou, Guoliang Dai, Chengyao Ma, Jiandong Zou, Meijuan Xu","doi":"10.1021/jasms.5c00259","DOIUrl":"https://doi.org/10.1021/jasms.5c00259","url":null,"abstract":"Depsipeptides, a structurally diverse class of nonribosomal peptides with broad bioactivities, present significant challenges for systematic characterization due to their complex fragmentation patterns in mass spectrometry (MS). This study aims to develop a generic three-step strategy based on high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) to facilitate the rapid screening and identification of both linear and cyclic depsipeptides. The workflow is defined by three sequential, logic-driven steps: (1) filtering potential depsipeptide precursors via diagnostic and adduct ions along with depsipeptide classification; (2) identifying the structural residues by monitoring diagnostic product ions and neutral losses; and (3) sequencing the peptide backbone through comprehensive analysis of MS/MS spectra. To validate the strategy's universality, it was applied to the analysis of depsipeptides in a complex biological matrix (extracts of Bombyx batryticatus). A total of 62 depsipeptides (encompassing octa-, hexa-, tetra-, and didepsipeptides, with both cyclic and linear topologies) were identified or tentatively characterized, including 34 potential novel analogs. Notably, the strategy successfully distinguished 10 methionine-containing depsipeptides with subtle redox modifications (native methionine, methionine sulfoxide, methionine sulfone), demonstrating its ability to resolve structurally similar derivatives. This three-step strategy offers a simple, rapid, and robust tool for comprehensive depsipeptide profiling. Its application to complex matrices highlights the strong potential for extending to other biological samples, advancing systematic analysis of depsipeptide families in natural products and biological systems.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Applications of DESI and DART Mass Spectrometry in Forensic Science. DESI和DART质谱法在法医学中的应用。

IF 2.7 2区化学

Journal of the American Society for Mass Spectrometry Pub Date : 2025-10-01 DOI: 10.1021/jasms.5c00175

Nathália Dos S Conceição, Alan R Pereira, Daniel S Trancoso, João Victor M de Almeida, Nicole Souza do Carmo, Nayara A Dos Santos, Hildegardo S França, Marc Yves Chalom, Wanderson Romão

{"title":"Applications of DESI and DART Mass Spectrometry in Forensic Science.","authors":"Nathália Dos S Conceição, Alan R Pereira, Daniel S Trancoso, João Victor M de Almeida, Nicole Souza do Carmo, Nayara A Dos Santos, Hildegardo S França, Marc Yves Chalom, Wanderson Romão","doi":"10.1021/jasms.5c00175","DOIUrl":"https://doi.org/10.1021/jasms.5c00175","url":null,"abstract":"Ambient Mass Spectrometry (AMS) has revolutionized forensic analysis by enabling rapid and direct detection of chemical compounds on complex surfaces with minimal or no sample preparation. Among AMS techniques, desorption electrospray ionization (DESI) and direct analysis in real time (DART) mass spectrometry have emerged as powerful analytical tools due to their speed, sensitivity, and versatility. This review examines the major applications of DESI and DART in forensic science, including the detection of explosives, gunshot residue, illicit drugs, inks, biological fluids, and latent fingerprints. The principles of each technique are briefly discussed, followed by a comparative analysis of their advantages, limitations, and performances in various forensic scenarios. Recent developments, practical considerations for implementation, and future perspectives are also addressed, highlighting the growing impact of DESI and DART in real-time forensic investigations and evidence processing.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Faces of Mass Spectrometry/Yan Wang. 质谱分析/王燕。

IF 2.7 2区化学

Journal of the American Society for Mass Spectrometry Pub Date : 2025-09-26 DOI: 10.1021/jasms.5c00313

Anne Brenner, J D Brookbank

引用次数: 0

SLIMPHONY: A SLIM-Based Instrument That Orchestrates Complex Ion Mobility-Mass Spectrometry Experiments. SLIMPHONY：一种基于细长的仪器，可协调复杂离子迁移-质谱实验。

IF 2.7 2区化学

Journal of the American Society for Mass Spectrometry Pub Date : 2025-09-26 DOI: 10.1021/jasms.5c00217

AnneClaire Wageman, Addison E Roush, Yuan Feng, Matthew F Bush

{"title":"SLIMPHONY: A SLIM-Based Instrument That Orchestrates Complex Ion Mobility-Mass Spectrometry Experiments.","authors":"AnneClaire Wageman, Addison E Roush, Yuan Feng, Matthew F Bush","doi":"10.1021/jasms.5c00217","DOIUrl":"https://doi.org/10.1021/jasms.5c00217","url":null,"abstract":"The inherent heterogeneity of biological macromolecules offers a unique challenge for analysis. The combination of ion mobility (IM) and mass spectrometry (MS) is sensitive to the size, shape, and dynamics of, for example, proteins and their complexes. Combining multiple dimensions of ion mobility and mass spectrometry (IM-IM-MS) while leveraging unique gas-phase manipulations between dimensions has great potential for increasing the information content for challenging analytes. Here, we introduce an instrument, SLIMPHONY, which was built using the Structures for Lossless Ion Manipulations (SLIM) architecture. SLIMPHONY is unique in that eight independently controlled traveling-wave regions work in concert to enable complex, multidimensional separations. Single-dimension IM-MS experiments were used to separate a mixture of protein and protein-complex ions and demonstrate that the peak-to-peak resolution increases roughly with the square root of the separation length for a pair of hexakis(fluoroalkoxy)phosphazine ions. Ion selection and trapping between dimensions was then used to probe the gas-phase unfolding of a subpopulation of ubiquitin ions. Finally, by varying the guard potential used to confine ions, we demonstrate tunable activation of ubiquitin subpopulations, which we analyzed using IM separations of various lengths. With the ability to select and activate ions in multiple regions, to vary the number of dimensions of IM, and to control the length of IM separation, SLIMPHONY is a flexible platform for characterizing protein ions.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Rapid Screening and Prioritization of Culture Conditions for Natural Product Discovery using the Liquid Microjunction Surface Sampling Probe. 利用液体微结表面采样探针快速筛选和优选天然产物发现的培养条件。

IF 2.7 2区化学

Journal of the American Society for Mass Spectrometry Pub Date : 2025-09-26 DOI: 10.1021/jasms.5c00193

Jessie F Deng, Jennifer L Kolwich, Georgia Reed, Rachel L Theriault, Haidy Metwally, Lainey Ennett, Chang Liu, Randy E Ellis, Avena C Ross, Richard D Oleschuk

{"title":"Rapid Screening and Prioritization of Culture Conditions for Natural Product Discovery using the Liquid Microjunction Surface Sampling Probe.","authors":"Jessie F Deng, Jennifer L Kolwich, Georgia Reed, Rachel L Theriault, Haidy Metwally, Lainey Ennett, Chang Liu, Randy E Ellis, Avena C Ross, Richard D Oleschuk","doi":"10.1021/jasms.5c00193","DOIUrl":"https://doi.org/10.1021/jasms.5c00193","url":null,"abstract":"The discovery of novel bioactive compounds remains a cornerstone of natural product (NP) chemistry. However, traditional NP discovery workflows are time- and resource-intensive, hindering sustainability and efficiency of multicondition screening projects. This study evaluates the application of the liquid microjunction surface sampling probe (LMJ-SSP) with partial least-squares discriminant analysis (PLS-DA) as a preliminary step in the NP discovery pipeline. By integrating ambient mass spectrometry with machine learning, we analyzed four strains of Penicillium fungi grown under 13 unique conditions in situ, without sample preparation. Using PLS-DA, we prioritized the growth conditions that maximized chemical diversity, offering insights into metabolite composition prior to resource-intensive steps in the NP discovery workflow. This LMJ-SSP-based approach achieved a significant reduction in sampling time (96%), overall cost (98%), and solvent consumption (98%)─streamlining the NP discovery pipeline through chemically informed prioritization and improved sustainability.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Retention Time Interpolation Enhances Peptide Mapping for HDX-MS. 保留时间插值增强HDX-MS的肽图谱。

IF 2.7 2区化学

Journal of the American Society for Mass Spectrometry Pub Date : 2025-09-26 DOI: 10.1021/jasms.5c00156

Damon Griffiths, Juan P Rincon Pabon, Charlotte Guffick, Argyris Politis

{"title":"Retention Time Interpolation Enhances Peptide Mapping for HDX-MS.","authors":"Damon Griffiths, Juan P Rincon Pabon, Charlotte Guffick, Argyris Politis","doi":"10.1021/jasms.5c00156","DOIUrl":"https://doi.org/10.1021/jasms.5c00156","url":null,"abstract":"Hydrogen/deuterium exchange mass spectrometry (HDX-MS) is a powerful technique for studying protein structural dynamics. A critical step in the HDX-MS workflow is generating a peptide map from nondeuterated samples, which serves as the reference for identifying and monitoring peptides in subsequent deuterium-labeled experiments. Maximizing peptide identifications improves sequence coverage and redundancy, enhancing the information content and spatial resolution of the HDX-MS data. However, peptide identification is often limited by suboptimal peptide separation/fragmentation. In other proteomic workflows, longer liquid chromatography (LC) gradients are commonly used to improve the peptide identification by increasing resolution. However, in HDX-MS workflows, such gradients are generally incompatible due to time constraints imposed by deuterium/hydrogen back-exchange. To address this, we introduce a flexible workflow that uses long-gradients during initial peptide mapping, followed by retention time (RT) interpolation for application in subsequent short-gradient HDX-MS. By performing both long- and short-gradient peptide mapping, we used shared peptides to generate a regression model that predicts short-gradient RTs for all peptides identified in the long-gradient experiment. This enables the use of the richer peptide maps provided by long-gradient chromatography without compromising the deuterium retention. The method is implemented by RTinterpolator, a freely available R script compatible with widely used HDX analysis platforms that rely on reference RT values for peptide monitoring in deuterium-labeled data. By providing predicted RTs aligned to short gradients, RTinterpolator offers a practical, accessible, and instrument-independent way of increasing sequence coverage and redundancy in HDX-MS experiments, particularly for large or complex proteins susceptible to the limitations of short-gradient chromatography.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Structural Elucidation of Phosphatidylcholines via Radical-Directed Dissociation of [M + Cu^II + Anion]⁺ Ion Types. 通过[M + CuII +阴离子]+离子类型的自由基定向解离研究磷脂酰胆碱的结构。

IF 2.7 2区化学

Journal of the American Society for Mass Spectrometry Pub Date : 2025-09-23 DOI: 10.1021/jasms.5c00197

Zunaira Naeem, Tingting Yan, Julia R Bonney, Troy R Scoggins, Boone M Prentice

{"title":"Structural Elucidation of Phosphatidylcholines via Radical-Directed Dissociation of [M + CuII + Anion]+ Ion Types.","authors":"Zunaira Naeem, Tingting Yan, Julia R Bonney, Troy R Scoggins, Boone M Prentice","doi":"10.1021/jasms.5c00197","DOIUrl":"https://doi.org/10.1021/jasms.5c00197","url":null,"abstract":"Tandem mass spectrometry (MS/MS) is frequently used in phospholipid characterization to determine lipid class, fatty acyl chain length, and degree of unsaturation. However, conventional MS/MS methods are limited in characterizing isomeric lipids resulting from variants in double bond and sn-positions within the fatty acyl chains. This limitation is due to the fact that conventional collision induced dissociation (CID) of even-electron lipid precursor ions does not generate highly efficient product ions from intrachain fragmentation of the fatty acyl substituents. Herein, we have developed a workflow that leverages a new lipid ion type to facilitate radical-directed dissociation (RDD). Briefly, low-energy CID of [M + CuII + anion]+ ion types results in a radical cation, and subsequent activation of the radical cation results in highly efficient intrachain fragmentation of fatty acyl chains. This method provides abundant diagnostic fragment ions that are associated with the double bond and fatty acyl chain positions on the glycerol backbone and thus can be used to differentiate isomeric phosphatidylcholines (PCs). The incorporation of an anionic ligand in the [PC + CuII + anion]+ ion type is key to this chemistry. Specifically, the major fragmentation channel for the [PC + CuI]+ ion type is neutral loss of phosphocholine headgroup but shifts to RDD for [PC + CuII + anion]+ ion types containing strongly electronegative anions.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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