MYELOPEROXIDASE-DERIVED 2-CHLOROHEXADECANAL FORMS SCHIFF BASES WITH

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大量研究表明髓过氧化物酶、炎症和动脉粥样硬化之间存在联系。MPO衍生的反应性氯化物种(RCS)攻击释放包括2-氯十六醛(2-ClHDA)在内的氯代脂肪醛(FALDs)的膜质原。？-氯-FALD的分子靶标尚不清楚。目前的研究证实了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仪，观察到氯化加合物为明显的席夫碱加合物。用氰化硼氢化钠还原这些席夫碱加合物，得到一种新的、稳定的加合物，通过消除HCl而产生。核磁共振进一步证实了这一结构。2-ClHDA与乙醇胺甘油磷脂的加合物也是磷脂酶D(PLD)的底物。2-ClHDA处理后的内皮细胞中观察到多种2-ClHDA-N修饰的乙醇胺甘油磷脂。这些结果显示了？-氯-FALD与伯胺的新型席夫碱加合物，这可能代表了？-氯-FALD的一个重要的命运。

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.