Tandem mass spectrometry of novel ether‐linked phospholipid analogs of anionic pulmonary surfactant phospholipids

Abstract

RATIONALE Structural analogs of the bioactive lipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol, were synthesized with a xylitol polar headgroup and both diacyl and diether radyl groups. Mass spectral characterization of xylitol phospholipids (PX) was carried out using collisional activation and high resolution mass measurements of positive molecular ion species and compared with the phosphatidylglycerol (PG) analogs. METHODS Xylitol phospholipids were synthesized using a transphosphatidylation reaction catalyzed by phospholipase D and purified by HPLC. Compounds were subjected to electrospray ionization and CID was performed using a tandem quadrupole mass spectrometer to generate positive and negative molecular ions. Diether phospholipids were additionally analyzed by high resolution mass spectrometry as protonated and sodiated molecular species in positive ion mode. RESULTS Ester linked xylitol phospholipid analogs behaved similar to PG after collisional activation of [M-H]−. The product ions formed by CID of the diether PG and PX negative ions only revealed information about the headgroup with no information about the aliphatic chains. In contrast, CID of protonated and sodiated diether phospholipid positive ions, revealed reactions corresponding to cleavage of the ether chain, likely occurring by charge driven reaction mechanisms. CONCLUSIONS Novel xylitol phospholipid analogs with diacyl and diether radyl substituents of the glycerol backbone were characterized by tandem mass spectrometry. These unique diether phospholipid analogs enabled exploration of ether cleavage reactions of the positive molecular ion species induced by collision induced decomposition.

The MYC Oncogene Cooperates with Sterol-Regulated Element-Binding Protein to Regulate Lipogenesis Essential for Neoplastic Growth

“…Significant PGS1 and PTPMT1 induction may preferentially promote CDP-DAG conversion to PGs, which could then shunt metabolites away from PI synthesis. One explanation is that MYC increases PIs in LC because of lung surfactants that are rich in both PGs and PIs (Agassandian and Mallampalli, 2013;Fickes et al, 2016;Griese et al, 1991). We infer that MYC generally increases PGs but differentially regulates other GPs, such as PIs, in a tissue-specific manner.…”

Experimental evidence that electrospray-produced sodiated lysophosphatidyl ester structures exist essentially as protonated salts

“…In a similar way, sodiated LGPE species in gas phase might exist as a charge-solvated structure when considering the canonical form and/or as a protonated salt structure from the zwitterion form (Scheme 1(c)). 6 In the literature, these cationized molecules are mainly considered as charge-solvated forms 7–10 rather than protonated salts. 3,5 Reasons for such a choice are often not discussed and as a consequence, proposed mechanisms to explain subsequent ion dissociation under low collision energy are generally considered as occurring by charge-remote fragmentation processes (i.e.…”

Mechanisms governing the fragmentation of glycerophospholipids containing choline and ethanolamine polar head groups

“…Such sodium retention has already been discussed. 36,38,46 Of particular interest are the very low abundance product ions at m/z 311.219 (and m/z 293.208 differing by a water molecule) and m/z 145.998. These two ions corresponding to complementary sodium-containing species are formed through several steps of precursor ion isomerization (RR IS and RR Hþ mechanisms) and cleavage into ID MAG intermediate with retention of the sodium of one or the other partner prior to their separation.…”

“…1,14,24,[26][27][28] Indeed, some of these mechanisms rather erroneously proposed at low energies implicitly consider, as commonly encountered under high energy conditions, that the charge is spectator of bond cleavages, representative of (i) thermal 15,29 and (ii) homolytic (resulting in radical induced cleavages) processes. [30][31][32][33][34][35] Under low-energy conditions, such dissociation processes can hardly be considered with the exception of cationized species with alkali [36][37][38] and transition metal ions. 39 Under low-energy conditions, charge-induced fragmentations are the preferred dissociation pathways.…”