Preparation of Nitrogen Analogues of Ceramide and Studies of Their Aggregation in Sphingomyelin Bilayers
Preparation of Nitrogen Analogues of Ceramide and Studies of Their Aggregation in Sphingomyelin Bilayers
复制标题
神经酰胺氮类似物的制备及其在鞘磷脂双层中的聚集研究
DOI：
10.1021/acs.langmuir.1c02101
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发表时间：
2021
期刊：
影响因子：
3.9
通讯作者：
Matsumori Nobuaki
中科院分区：
文献类型：
--
作者：
Yasuda Hiroki;Torikai Kohei;Kinoshita Masanao;Sazzad Md. Abdullah Al;Tsujimura Koya;Slotte J. Peter;Matsumori Nobuaki
神经酰胺可能通过在脂质双层中形成横向分离和高度堆积的富含神经酰胺的结构域来调节生物过程。在其类似物的制备过程中，我们发现C1位的氢键活性官能团对于在脂质双层中形成富含神经酰胺的结构域是必要的[Matsufuji; Langmuir 2018]。因此，在本研究中，我们新合成了三种神经酰胺类似物：CerN 3，CerNH 2和CerNHAc，其中神经酰胺的1-OH基团被氮官能团取代。CeNH 2和CeNHAc能够在它们的头基中形成氢键，而CeN 3不能。荧光显微镜观察和差示扫描量热法分析表明，这些神经酰胺类似物形成神经酰胺丰富的相在鞘磷脂双层，虽然它们的热稳定性略差于正常的神经酰胺。此外，广角X射线衍射分析表明，富CerNHAc和CerN 3相的链堆积结构与普通神经酰胺相似，而富CerNH 2相由于形成了CerNH 3+而显示出略微松散的链堆积。虽然由于头基中缺乏氢键能力，CerN 3的畴形成是出乎意料的，但由于其拉曼活性和点击化学的适用性，它可能成为研究富含神经酰胺的相和神经酰胺相关的生物功能之间的机械联系的有前途的工具。
Ceramides can regulate biological processes probably through the formation of laterally segregated and highly packed ceramide-rich domains in lipid bilayers. In the course of preparation of its analogues, we found that a hydrogen-bond-competent functional group in the C1 position is necessary to form ceramide-rich domains in lipid bilayers [Matsufuji;Langmuir2018]. Hence, in the present study, we newly synthesized three ceramide analogues: CerN3, CerNH2, and CerNHAc, in which the 1-OH group of ceramide is substituted with a nitrogen functionality. CerNH2and CerNHAc are capable of forming hydrogen bonds in their headgroups, whereas CerN3is not. Fluorescent microscopy observation and differential scanning calorimetry analysis disclosed that these ceramide analogues formed ceramide-rich phases in sphingomyelin bilayers, although their thermal stability was slightly inferior to that of normal ceramides. Moreover, wide-angle X-ray diffraction analysis showed that the chain packing structure of ceramide-rich phases of CerNHAc and CerN3was similar to that of normal ceramide, while the CerNH2-rich phase showed a slightly looser chain packing due to the formation of CerNH3+. Although the domain formation of CerN3was unexpected because of the lack of hydrogen-bond capability in the headgroup, it may become a promising tool for investigating the mechanistic link between the ceramide-rich phase and the ceramide-related biological functions owing to its Raman activity and applicability to click chemistry.