TY - JOUR
T1 - Preparation and Membrane Properties of Oxidized Ceramide Derivatives
AU - Matsufuji, Takaaki
AU - Kinoshita, Masanao
AU - Möuts, Anna
AU - Slotte, J. Peter
AU - Matsumori, Nobuaki
N1 - Funding Information:
We thank Prof. Tohru Oishi for letting us use the mass spectrometer. This work was supported in part by Grants-in-Aid for scientific research from the Japan Society for the Promotion of Science Kiban B (15H03121), Grants-in-Aid for Innovative Areas from the Japan Society for the Promotion of Science (26102527 and 16H00773), and the Lipid Active Structure Project supported by Exploratory Research for Advanced Technology Organization of the Japan Science and Technology Agency. The Slotte laboratory was supported by grants from the Jane and Aatos Erkko Foundation and the Sigrid Juselous Foundation.
PY - 2018/1/9
Y1 - 2018/1/9
N2 - Ceramide is a bioactive lipid with important roles in several biological processes including cell proliferation and apoptosis. Although 3-ketoceramides that contain a keto group in place of the 3-OH group of ceramide occur naturally, ceramide derivatives oxidized at the primary 1-OH group have not been identified to date. To evaluate how the oxidative state of the 1-OH group affects the physical properties of membranes, we prepared novel ceramide derivatives in which the 1-OH group was oxidized to a carboxylic acid (PCerCOOH) or methylester (PCerCOOMe) and examined the rigidity of their monolayers and the formation of gel domains in palmitoyloleoylphosphatidylcholine (POPC) or sphingomyelin (SM) bilayers. As a result, PCerCOOH and PCerCOOMe exhibited membrane properties similar to those of native ceramide, although the deprotonated form of PCerCOOH, PCerCOO-, exhibited markedly lower rigidity and higher miscibility with POPC and SM. This was attributed to the electrostatic repulsion of the negative charge, which hampered the formation of the ceramide-enriched gel domain. The similarities in the properties of PCerCOOMe and ceramide revealed the potential to introduce various functional groups onto PCerCOOH via ester or amide linkages; therefore, these derivatives will also provide a new strategy for developing molecular probes, such as fluorescent ceramides, and inhibitors of ceramide-related enzymes.
AB - Ceramide is a bioactive lipid with important roles in several biological processes including cell proliferation and apoptosis. Although 3-ketoceramides that contain a keto group in place of the 3-OH group of ceramide occur naturally, ceramide derivatives oxidized at the primary 1-OH group have not been identified to date. To evaluate how the oxidative state of the 1-OH group affects the physical properties of membranes, we prepared novel ceramide derivatives in which the 1-OH group was oxidized to a carboxylic acid (PCerCOOH) or methylester (PCerCOOMe) and examined the rigidity of their monolayers and the formation of gel domains in palmitoyloleoylphosphatidylcholine (POPC) or sphingomyelin (SM) bilayers. As a result, PCerCOOH and PCerCOOMe exhibited membrane properties similar to those of native ceramide, although the deprotonated form of PCerCOOH, PCerCOO-, exhibited markedly lower rigidity and higher miscibility with POPC and SM. This was attributed to the electrostatic repulsion of the negative charge, which hampered the formation of the ceramide-enriched gel domain. The similarities in the properties of PCerCOOMe and ceramide revealed the potential to introduce various functional groups onto PCerCOOH via ester or amide linkages; therefore, these derivatives will also provide a new strategy for developing molecular probes, such as fluorescent ceramides, and inhibitors of ceramide-related enzymes.
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U2 - 10.1021/acs.langmuir.7b02654
DO - 10.1021/acs.langmuir.7b02654
M3 - Article
C2 - 29231736
AN - SCOPUS:85040307838
VL - 34
SP - 465
EP - 471
JO - Langmuir
JF - Langmuir
SN - 0743-7463
IS - 1
ER -