Lithium Hydroxide Hydrolysis Combined with MALDI TOF Mass Spectrometry for Rapid Sphingolipid Detection

Tran, Anh; Wan, Liting; Xu, Zhenbo; Haro, Janette M; Li, Bing; Jones, Jace W.

doi:10.1021/jasms.0c00322

Cited by 11 publications

(15 citation statements)

References 85 publications

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“…The multiadduct phenomenon complicates lipid identification and potentially reduces sensitivity by splitting analyte signal across the ion series. The addition of an exogenous alkali metal source to the MALDI matrix can alleviate the issue of multiadduction, and in the case of lithium chloride (LiCl), lithium adduct consolidation is promoted . Also, the use of THAP as the MALDI matrix in combination with LiCl was shown to be superior for lithium adduction compared to other common matrices including DHB. , With this in mind, we analyzed the IVA lipid extract using THAP plus 10 mM of LiCl (THAP + Li) as the MALDI matrix.…”

Section: Resultsmentioning

confidence: 99%

“…The addition of an exogenous alkali metal source to the MALDI matrix can alleviate the issue of multiadduction, and in the case of lithium chloride (LiCl), lithium adduct consolidation is promoted . Also, the use of THAP as the MALDI matrix in combination with LiCl was shown to be superior for lithium adduction compared to other common matrices including DHB. , With this in mind, we analyzed the IVA lipid extract using THAP plus 10 mM of LiCl (THAP + Li) as the MALDI matrix. The resulting AP-MALDI HRMS spectrum clearly showed the benefits of lithium adduct consolidation for decreasing spectral complexity and increasing detection sensitivity (Figure B).…”

Section: Resultsmentioning

confidence: 99%

“…MALDI MS is also compatible with high-resolution mass spectrometers, amenable to automation, and complementary to ESI platforms . Our laboratory has recently demonstrated the effectiveness of using lithium adduct consolidation on a MALDI MS platform for increased sensitivity and decreased spectral complexity for lipid detection . The matrix combination of 2′,4′,6′-trihydroxyacetophenone and lithium (THAP + Li) effectively forced lithium adduct consolidation during the MALDI process, resulting in reduced spectral complexity and enhanced lipid detection, especially for sphingolipids.…”

Section: Introductionmentioning

confidence: 99%

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Rapid Detection of Viral Envelope Lipids Using Lithium Adducts and AP-MALDI High-Resolution Mass Spectrometry

Tran

Monreal

Moskovets

et al. 2021

J. Am. Soc. Mass Spectrom.

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There is an unmet need to develop analytical strategies that not only characterize the lipid composition of the viral envelope but also do so on a time scale that would allow for high-throughput analysis. With that in mind, we report the use of atmospheric pressure (AP) matrix-assisted laser desorption/ionization (MALDI) high-resolution mass spectrometry (HRMS) combined with lithium adduct consolidation to profile total lipid extracts rapidly and confidently from enveloped viruses. The use of AP-MALDI reduced the dependency of using a dedicated MALDI mass spectrometer and allowed for interfacing the MALDI source to a mass spectrometer with the desired features, which included high mass resolving power (>100000) and tandem mass spectrometry. AP-MALDI combined with an optimized MALDI matrix system, featuring 2′,4′,6′-trihydroxyacetophenone spiked with lithium salt, resulted in a robust and high-throughput lipid detection platform, specifically geared to sphingolipid detection. Application of the developed workflow included the structural characterization of prominent sphingolipids and detection of over 130 lipid structures from Influenza A virions. Overall, we demonstrate a high-throughput workflow for the detection and structural characterization of total lipid extracts from enveloped viruses using AP-MALDI HRMS and lithium adduct consolidation.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rapid Detection of Viral Envelope Lipids Using Lithium Adducts and AP-MALDI High-Resolution Mass Spectrometry

Tran

Monreal

Moskovets

et al. 2021

J. Am. Soc. Mass Spectrom.

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“…Viral membrane lipids were extracted using a modi ed liquid-liquid extraction procedure as described previously [75]. Extracted lipids were analyzed by LC-MS/MS, as described previously [76].…”

Section: Methodsmentioning

confidence: 99%

New Class of Broad-Spectrum Antivirals Improves Influenza Virus Vaccine Development

Pacheco

Buchholz

Monreal

et al. 2022

Preprint

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Enveloped viruses can cause devastating zoonotic diseases and are the most likely to cause global pandemics. We identified a new class of small-molecule sulfur-containing antiviral compounds (XM series) that broadly inhibit enveloped viruses. The antivirals’ mechanism of action was explored via various multidisciplinary approaches, concluding that the XM antivirals alter membrane lipid chemical compositions, increase membrane order deep within the hydrophobic region of the bilayer, and increase membrane phase transition temperatures. Such effects cause inhibition of membrane fusion and viral entry, while leaving the viral glycoproteins and genomes largely unaffected. Consequently, we tested whether these features would lead to effective whole inactivated enveloped virus vaccines. As a proof-of-principle, we generated an inactivated influenza virus (IIV) vaccine using compound XM-01 (XM-01-IIV). We compared this new vaccine to traditional paraformaldehyde-inactivated, to control compound-inactivated, and to live virus vaccines, using a mouse model of disease. Excitingly, compared to a traditional IIV vaccine, XM-01-IIV vaccination improved neutralizing antibody responses against both hemagglutinin and neuraminidase, and decreased mouse morbidity and mortality following influenza virus challenge. Therefore, this study uncovers a novel class of broadly acting antivirals that enhances influenza virus vaccine development and offers great potential for broadly generating future highly-potent inactivated enveloped virus vaccines.

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“…[17] [20] The MALDI-TOF MS of the lithiated species such as fatty acids, lipids, phospholipids, sphingolipid, wax, and hydrocarbons have been performed and the SME effect has been observed. [14,18,[22][23][24] and [M + nLi] + (n = 1, 2, 3, and 4 or more) and [M-H + 2Li] + species were detected.…”

Section: Introductionmentioning

confidence: 99%

Sodium salts effect on the time of flight mass spectra of some amino acids in the direct‐laser desorption ionization and matrix‐assisted laser desorption/ionization

Amiri

Farrokhpour

Tabrizchi

2021

J Chinese Chemical Soc

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One of the problems in the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) of small molecules is the overlap between the peaks originated from the matrix and analyte. The MALDI and the direct laser desorption ionization (direct-LDI) spectrum of the phenylalanine amino acid (FAA) has been recorded and assigned in the absence and presence of the salts, including NaF and NaOH. It was seen that the peaks originated from the matrix were suppressed in the MALDI spectrum of the FFA in the presence of salt. In addition, the salt effect on the TOF mass spectrum of the FAA, recorded by the direct-LDI, was investigated. The mass spectrum of the FFA, in the presence of NaF, showed a relatively strong and sharp peak assigned to [FAA-H + 2Na] + species in both the direct-LDI and MALDI. The direct-LDI spectrum was less crowded than the MALDI spectrum. The same results were obtained when NaOH was used instead of NaF. The peak related to [Amino acid-H + 2Na] + species was considered a characteristic peak in both the direct-LDI and MALDI of the selected amino acids in the presence of NaF and NaOH.

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Lithium Hydroxide Hydrolysis Combined with MALDI TOF Mass Spectrometry for Rapid Sphingolipid Detection

Cited by 11 publications

References 85 publications

Rapid Detection of Viral Envelope Lipids Using Lithium Adducts and AP-MALDI High-Resolution Mass Spectrometry

Rapid Detection of Viral Envelope Lipids Using Lithium Adducts and AP-MALDI High-Resolution Mass Spectrometry

New Class of Broad-Spectrum Antivirals Improves Influenza Virus Vaccine Development

Sodium salts effect on the time of flight mass spectra of some amino acids in the direct‐laser desorption ionization and matrix‐assisted laser desorption/ionization

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