MYELOPEROXIDASE-DERIVED 2-CHLOROHEXADECANAL FORMS SCHIFF BASES WITH

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 许多研究表明髓过氧化物酶、炎症和动脉粥样硬化之间存在关系。MPO衍生的反应性氯化物质（RCS）攻击膜缩醛，释放包括2-氯十六烷醛（2-ClHDA）在内的<$-氯-脂肪醛（<$-Cl-FATIGUE Ds）。尚不清楚戊-氯-β-D的分子靶点。目前的研究表明2-ClHDA与乙醇胺甘油磷脂和Fmoc-赖氨酸的加合物。利用电喷雾电离质谱，观察到氯化加合物是明显的席夫碱加合物。这些希夫碱加合物与氰基硼氢化钠的还原导致了一种新的，稳定的加合物产生的消除HCl。NMR进一步证实了该结构。2-ClHDA与乙醇胺甘油磷脂的加合物也是磷脂酶D（PLD）的底物。水解产物衍生为五氟苯甲酰基酯，并通过气相色谱进一步确认其结构女士在用2-ClHDA处理的内皮细胞中观察到2-ClHDA-N-修饰的乙醇胺甘油磷脂的多个分子种类。这些结果表明，新的席夫碱加合物的<$-Cl-β-D的伯胺，这可能是一个重要的命运<$-Cl-β-D。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Numerous studies have suggested relationships between myeloperoxidase, inflammation, and atherosclerosis. MPO-derived reactive chlorinating species (RCS) attack membrane plasmalogens releasing ¿-chloro-fatty aldehydes (¿-Cl-FALDs) including 2-chlorohexadecanal (2-ClHDA). The molecular targets of ¿-Cl-FALDs are not known. The current study demonstrates 2-ClHDA adducts with ethanolamine glycerophospholipids and Fmoc-lysine. Utilizing electrospray ionization mass spectrometry, chlorinated adducts were observed that are apparent Schiff base adducts. Reduction of these Schiff base adducts with sodium cyanoborohydride resulted in a novel, stable adduct produced by the elimination of HCl. NMR further confirmed this structure. 2-ClHDA adducts with ethanolamine glycerophospholipids were also substrates for phospholipase D (PLD). The hydrolysis products were derivatized to pentafluorobenzoyl esters, and further structurally confirmed by GCMS. Multiple molecular species of 2-ClHDA-N-modified ethanolamine glycerophospholipids were observed in endothelial cells treated with 2-ClHDA. These results show novel Schiff base adducts of ¿-Cl-FALDs with primary amines, which may represent an important fate of ¿-Cl-FALDs.