US EPA

7417578 

Journal Article 

N-cholesteryl sphingomyelin-A synthetic sphingolipid with unique membrane properties 

Sergelius, C; Yamaguchi, S; Yamamoto, T; Slotte, JP; Katsumura, S; , 

2011 

1 

Biochimica et Biophysica Acta
ISSN: 0006-3002
EISSN: 1878-2434 

ELSEVIER SCIENCE BV 

AMSTERDAM 

1808 

4 

1054-1062 

English 

21194522 

10.1016/j.bbamem.2010.12.021 

WOS:000289135300005 

https://linkinghub.elsevier.com/retrieve/pii/S0005273610004566
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A sphingomyelin chimera in which the amide-linked acyl chain was replaced with cholesterol carbamate was prepared and its properties examined. The sphingomyelin/cholesterol chimera (N-cholesterol-D-erythro-sphingomyelin) was able to form unilamellar vesicles of defined size when extruded through 200nm pore size membranes. These N-cholesteryl sphingomyelin bilayers were resistant to solubilization by Triton X-100. When N-cholesteryl sphingomyelin was added to N-palmitoyl sphingomyelin (N-palmitoyl-d-erythro-sphingomyelin) bilayers, it increased acyl chain order as determined by 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy. N-cholesteryl sphingomyelin was, however, not as good an inducer of membrane order compared to cholesterol on a molar basis. Differential scanning calorimetry studies further showed that the miscibility of N-cholesteryl sphingomyelin with N-palmitoyl-d-erythro-sphingomyelin bilayers was non-ideal, and the effect of N-cholesteryl sphingomyelin on the N-palmitoyl-d-erythro-sphingomyelin gel-fluid transition enthalpy differed from that seen with cholesterol. Together with N-palmitoyl-d-erythro-sphingomyelin, the N-cholesteryl sphingomyelin chimera was able to form sterol-enriched ordered domains in a fluid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer. N-cholesteryl sphingomyelin in the absence of N-palmitoyl-d-erythro-sphingomyelin was unable to form such sterol-enriched ordered domains in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer. However, N-cholesteryl sphingomyelin markedly increased the affinity of cholestatrienol for N-cholesteryl sphingomyelin containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers, suggesting that N-cholesteryl sphingomyelin was able to somehow stabilize sterol interaction in fluid bilayers. Based on our results, we conclude that N-cholesteryl sphingomyelin behaved more like a cholesterol than a sphingolipid in fluid bilayer membranes. Because N-cholesteryl sphingomyelin increased bilayer order, conferred resistance against detergent solubilization, and is not degradable by phospholipases A(2), it could constitute a good lipocomplex matrix for drug delivery vehicles. 

Cholestatrienol; Fluorescence quenching; Lateral domains; Membrane solubilization; Membrane structure; cholesterol; liposome; n cholesterylsphingomyelin; n palmitoyl dextro erythro sphingomyelin; sphingomyelin; triton x 100; unclassified drug; anisotropy; article; binding affinity; biodegradability; chimera; conformational transition; controlled study; covalent bond; differential scanning calorimetry; drug delivery system; drug solubility; enthalpy; lipid analysis; membrane binding; membrane biology; membrane structure; membrane vesicle; phospholipid bilayer; priority journal; Calorimetry, Differential Scanning; Cholesterol; Fluorescence Polarization; Lipid Bilayers; Octoxynol; Solubility; Spectrophotometry; Sphingolipids; Sphingomyelins; Temperature; Unilamellar Liposomes