- 著者
- Toshiaki Taira Yuki Ishizaki Shusei Yamamoto Kenichi Sakai Hideki Sakai Tomohiro Imura
- 出版者
- Japan Oil Chemists' Society
- 雑誌
- Journal of Oleo Science (ISSN:13458957)
- 巻号頁・発行日
- vol.68, no.12, pp.1223-1230, 2019 (Released:2019-12-01)
- 参考文献数
- 42
- 被引用文献数
- 1 1
We report the synthesis of amphiphilic dodecenyl phosphonic acid PC12 from vinylphosphonic acid, a reactive phosphonic acid intermediate. The trans-P-C=C moiety enabled PC12 to disperse well in water. Surface tension and dynamic light scattering measurements revealed that PC12 exhibited high surface activity and reduced the surface tension of water from 72.0 to 23.6 mN/m, thereby resulting in the spontaneous formation of aggregates even in a dilute aqueous solution (critical aggregation concentration (CAC) = 4.8 × 10–4 M). In contrast to modern lipids with double-tailed structures, the PC12 of simple singletailed structure spontaneously formed bilayered vesicles, without an external energy supply. Compared with the strength of hydrogen bonds formed by the long, saturated alkyl chain of dodecyl phosphonic acid (DPA), the strength of PC12 intermolecular hydrogen bonds was weaker. The melting point of PC12 was approximately 20°C lower than that of DPA. These results indicate that the trans-P-C=C moiety was considerably important for spontaneous vesicle formation in water. Preliminary modeling of the morphological transitions of the closed bilayer structures in the vesicles was then conducted, by varying the pH and adding an α-helical peptide scaffold.
- 著者
- Keiko KOBAYASHI Yuki ISHIZAKI Shosuke KOJO Hiroe KIKUZAKI
- 出版者
- Center for Academic Publications Japan
- 雑誌
- Journal of Nutritional Science and Vitaminology (ISSN:03014800)
- 巻号頁・発行日
- vol.62, no.2, pp.123-129, 2016 (Released:2016-06-03)
- 参考文献数
- 30
- 被引用文献数
- 3 6
Sphingomyelinases (SMases) are key enzymes involved in many diseases which are caused by oxidative stress, such as atherosclerosis, diabetes mellitus, nonalcoholic fatty liver disease, and Alzheimer’s disease. SMases hydrolyze sphingomyelin to generate ceramide, a well-known pro-apoptotic lipid. SMases are classified into five types based on pH optimum, subcellular localization, and cation dependence. Previously, we demonstrated that elevation of secretory sphingomyelinase (sSMase) activity increased the plasma ceramide concentration under oxidative stress induced by diabetes and atherosclerosis in murine models. These results suggest that sSMase inhibitors can prevent the progress of these diseases. The present study demonstrated that sSMase activity was activated by oxidation and inhibited by reduction. Furthermore, we examined whether catechins inhibited the sSMase activity in a physiological plasma concentration. Among catechins, (−)-epicatechin 3-O-gallate (ECg) exhibited strong inhibitory effect on sSMase (IC50=25.7 μM). This effect was attenuated by methylation at the 3″- or 4″-position. On the other hand, (−)-epigallocatechin 3-O-gallate (EGCg) and (−)-catechin 3-O-gallate (Cg) exhibited weaker inhibitory activity than ECg, and (−)-epicatechin and (−)-epigallocatechin did not affect sSMase activity. Additionally, one synthetic catechin, (−)-3′-O-methylepigallocatechin 3-O-gallate (EGCg-3′-O-Me), showed the strongest inhibitory effect (IC50=1.7 μM) on sSMase. This phenomenon was not observed for (−)-4′-O-methylepigallocatechin 3-O-gallate. These results suggest that the reduction potential, the presence of the galloyl residue at the C-3 position, and the steric requirement to interact with sSMase protein are important for effective inhibition of sSMase.