Rapid tin-mediated access to a lysophosphatidylethanolamine (LPE) library: Application to positional LC/MS analysis for hepatic LPEs in non-alcoholic steatohepatitis model mice

Abstract

Abstract. Even though lysophospholipids have attracted much interest in recent years on account of their unique bioactivity, research related to lysophospholipids is usually hampered by problems associated with standard sample preparation and discrimination of regioisomers. Herein, we demonstrate a quick tin-chemistry-based synthetic route to lysophosphatidylethanolamines (LPEs) and its application in the positional analysis of hepatic LPEs in non-alcoholic steatohepatitis (NASH) model mice. We found that the preference of hepatic LPE regioisomer largely depends on the unsaturation of acyl chain in both control and NASH model mice. In addition, hepatic C18:2-LPE and C20:5-LPE levels were significantly lower in the NASH model mice than those in the control. The LC/MS technique based on the library of LPE regioisomers allows an accurate observation of hepatic LPE metabolism and might provide useful information to elucidate yet ambiguous pathogenesis of NASH.2

A Simple and Efficient Method for Synthesis of sn‐Glycero‐Phosphoethanolamine

“…The reaction mixture was concentrated under reduced pressure and resulting mixture was purified by flash column chromatography (CHCl 3:MeOH = 1:0~20:1, by vol) to give Tr-DPPE 2 (122 mg, 91%) as a white solid. The 1 H-NMR and 13 C-NMR of the compound were identical to our previous report (Furukawa et al 2016) (See Supporting Information). Rf = 0.42 (CHCl3:MeOH = 7:1, by vol); 1 H-NMR (400 MHz, CDCl3) δ 7.53-7.24 (m, 15 H), 5.14 (br m, 1 H), 4.32-4.29 (br d, 1 H, J = 11.3 Hz), 4.12-4.08 (br m, 2 H), 3.82 (br m, 2 H), 3.04 (br s, 1 H), 2.22-2.15 (br m, 4 H), 1.56 (br s, 4 H), 1.24 (br s, 48 H), 0.9-0.84 (t, 6 H, J = 6.6 Hz); 13 C-NMR (100 MHz, CDCl3) δ 173.…”

“…In our previous study involving synthesis of lyso-PE, we found that protection of amine group is necessary to carry out the direct alkali hydrolysis of DPPE (Furukawa et al 2016). More specifically, trityl protection of primary amine of GroPEtn makes the N-trityl bond more stable during the synthesis and it is successfully employed in a previous PE and lyso-PE synthesis (Furukawa et al 2016). A three-step semisynthetic approach for the synthesis of GroPEtn employed in the current study is shown in Figure 1.…”

“…The protection of an amine group of DPPE 1, is carried out with tritylbromide to obtain N-trityl-DPPE 2, and the subsequent deacylation using Zemplen conditions afforded the desired N-trityl-GroPEtn 3, in 90% yield (Furukawa et al 2016). The deacylation is carried out under alkali conditions using sodium methoxide (2.2 eq) in a slight excess amount to the previous method to accomplish the reaction towards completion and obtain a good yield.…”

“…GroPEtn showed the enhanced activity of epidermal growth factor in cultured hepatocytes (Nelson et al 1996). Even though several methods for synthesis of PE and lyso-PE were reported (Rakhit et al 1969;Furukawa et al 2016;D'Arrigo and Servi 2010) there are no reports on the efficient synthesis of GroPEtn.…”

An Efficient Glycoblotting‐Based Analysis of Oxidized Lipids in Liposomes and a Lipoprotein

“…Combatting these often deleterious phenomena requires the development of efficient analytical systems. Our and other groups have previously reported protocols to analyze oxidized lipids by liquid chromatography/mass spectrometry (LC/MS) techniques– and carbon nanotube sensors ,. Although the LC/MS‐based approach is a useful method for untargeted lipidomics, high‐throughput methods are preferable for clinical or medicinal applications …”