Gas phase derivatization for lipidomic MS analysis

用于脂质组学 MS 分析的气相衍生化

基本信息

批准号：
7268633
负责人：
JAMES T. BRENNA
金额：
$ 23.77万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7268633
关键词：
Acetonitriles Acids Americas Analytical Chemistry Animals Anti-Obesity Agents Anticarcinogenic Agents Area Atmospheric Pressure Automation Award Biological Biomedical Research Carbon Characteristics Charge Chemicals Chemistry Cholesterol Esters Class Collaborations Complex Condition Conjugated Linoleic Acids Coupled Data Development Diagnostic Dissociation Electronics Electrons Electrospray Ionization Environment Esters Ethylene Oxide Fatty Acids Fatty acid glycerol esters Food Food Processing Food Supply Fourier Transform Gases Generations Glycerol Goals Harvest Human Image Ions Isomerism Laboratories Lasers Length Lipids Liquid substance Literature Mass Spectrum Analysis Methods Methylamines Molecular Names Nobel Prize Nutritional status Object Attachment Paper Parents Peripheral Phase Phospholipids Polyunsaturated Fatty Acids Positioning Attribute Principal Investigator Process Protons Public Health Publications Publishing Rate Reaction Reagent Reporting Research Research Personnel Resources Rumen Scanning Scientist Series Side Solid Solvents Spectrometry Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Staging Standards of Weights and Measures Stream Structure Surface Techniques Time Tissues Today Triglycerides United States Food and Drug Administration United States National Academy of Sciences Unsaturated Fatty Acids Work Writing acyl group adduct base carbene chemical reaction dalton dietary supplements driving force expectation fatty acid metabolism innovation instrument ionization ionization technique mass spectrometer member methylamine molecular mass novel physical science professor programs small molecule

项目摘要

DESCRIPTION (provided by applicant): Lipidomic approaches now gaining acceptance are based on the rapid, comprehensive mass spectrometry (MS) analysis of carbon length and degree of unsaturation in fatty acyl groups and their positions (regiospecificity) at the sn 1,2, or 3 positions of glycerolipids. The most important analytical issue facing lipidomic analysis is that no general method has emerged that delivers double bond position in the fatty acyl groups simultaneously with regiospecific information, We propose to exploit a novel mass spectrometric method developed in our laboratory that should enable complete, automated characterization of all acylated lipids in crude lipid extracts, Ion-molecule reactions that result in adducts during chemical ionization (Cl) mass spectrometry (MS) are effectively a gas phase derivatization process. In a series of 8 papers since 1999, we reported co-discovery of gas derivatization of unsaturated fatty acid methyl esters (FAME) by acetonitrile CI/MS/MS. Fragmentation of the resulting adducts provides the first rapid, convenient structural analysis of FAME. Acetonitrile CI produces an ion at m/z 54 which adds covalently across double bonds; the resulting [M+54]+ ion undergoes charge-driven fragmentation upon collisional activation to yield diagnostic ions that unequivocally establish the position of double bonds in polyunsaturates. Recently, this reaction has been observed for atmospheric pressure CI in a liquid stream. We propose a two pronged approach where we 1) develop APCI based on acetonitrile for analysis of double bond position for fatty acyl groups within lipid classes derived from crude lipid extracts, and 2) complete development of acetonitrile GClCIIMSlMS to include analysis of all polyunsaturated non-methylene-interrupted fatty acids. These goals will eventually be coupled, and together with conventional MS/MS modes (precursor, product, and neutral loss scans), analysis of gas phase derivatized acyl-containing compounds should provide complete structural and quantitative information for most glycerolipids and can be automated for lipidomic analysis.

描述（由申请人提供）：现在获得接受的脂质细胞学方法基于脂肪酰基基团的碳长度和不饱和度的快速，全面的质谱法（MS）分析及其在SN 1,2或甘油脂脂的3个位置处的脂肪酰基基团及其位置（Regiospificities）。脂科学分析面临的最重要的分析问题是，没有出现一般方法，该方法与脂肪酰基基团在脂肪酰基组中提供双重键位，并同时与型型信息信息相同，我们建议在我们的实验室中开发的新型质谱方法，该方法应启用所有化合物在化合物中的自动化脂质的自动化，以使其在化合物中进行自动化，以使其在化合物中进行构构构构，以构构构构构构构构，以构构的构构构构构构构构构构构构构构构构构构构构构构构构构构构构构构构。（CL）质谱（MS）实际上是气相衍生过程。自1999年以来，在一系列8篇论文中，我们报道了乙腈CI/MS/MS对不饱和脂肪酸甲酯（FAME）的气体衍生物共发现。产生的加合物的碎片提供了第一个快速，方便的成名结构分析。乙腈CI以m/z 54的形式产生一个离子，该离子在双键之间共价。产生的[M+ 54]+离子在碰撞激活后经历了电荷驱动的碎片，以产生诊断离子，这些诊断离子明确地建立了双键在多不饱和度中的位置。最近，已经观察到了液体流中大气压力CI的反应。我们提出了一种两种统治方法，其中我们1）基于乙腈开发APCI，用于分析脂肪酰基在脂质类中的双键位置，这些脂肪酰基在源自粗脂质提取物的脂质类别中，以及2）完全开发乙腈GCLCIIMSLMS，包括分析所有多不合同的非甲基化脂肪脂肪酸脂肪酸的分析。这些目标最终将耦合，并与常规的MS/MS模式（前体，产品和中性损失扫描）一起，对含酰基酰基的化合物的分析应为大多数甘油脂质提供完整的结构和定量信息，并可以自动化以进行自动化脂质分析。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

On the formation of conjugated linoleic acid diagnostic ions with acetonitrile chemical ionization tandem mass spectrometry.

DOI：
10.1002/rcm.1797
发表时间：
2005-02
期刊：
Rapid communications in mass spectrometry : RCM
影响因子：
0
作者：
A. L. Michaud;P. Lawrence;R. Adlof;J. T. Brenna
通讯作者：
A. L. Michaud;P. Lawrence;R. Adlof;J. T. Brenna

Branched chain fatty acids are constituents of the normal healthy newborn gastrointestinal tract.

DOI：
10.1203/pdr.0b013e318184d2e6
发表时间：
2008-12
期刊：
Pediatric research
影响因子：
3.6
作者：
Ran-Ressler RR;Devapatla S;Lawrence P;Brenna JT
通讯作者：
Brenna JT

Alternative splicing generates a novel FADS2 alternative transcript in baboons.

DOI：
10.1007/s11033-009-9750-9
发表时间：
2010-06
期刊：
Molecular biology reports
影响因子：
2.8
作者：
Park WJ;Reardon HT;Tyburczy C;Kothapalli KS;Brenna JT
通讯作者：
Brenna JT

Milk fat synthesis is unaffected by abomasal infusion of the conjugated diene 18:3 isomers cis-6,trans-10, cis-12 and cis-6,trans-8,cis-12.

乳脂合成不受共轭二烯 18:3 异构体 cis-6、trans-10、cis-12 和 cis-6、trans-8、cis-12 皱胃输注的影响。

DOI：
10.1007/s11745-005-1363-7
发表时间：
2005
期刊：
Lipids
影响因子：
1.9
作者：
Saebø,A;Perfield2nd,JW;Delmonte,P;Yurawecz,MP;Lawrence,P;Brenna,JT;Bauman,DE
通讯作者：
Bauman,DE