TY - JOUR
T1 - The synthesis and molecular dynamics of phospholipids having hydroxylated fatty acids at the sn-2 position
AU - Isaacson, Yisrael
AU - Sherbourne, Caroline D.
AU - Gross, Richard W.
AU - Stenson, William F.
N1 - Funding Information:
This research was supported by a grant from the National Foundation for Ileitis and Colitis and by grants DK33165, HL34839 and DK33487 from the NIH. Mass spectrometry data were obtained at the Washington University Mass Spectrometry Resource, which is supported by a grant from the National Institutes for Health (RR00954). R.W.G. is an Established Investigator of the American Heart Association.
PY - 1990/2
Y1 - 1990/2
N2 - We have devised a general method for the synthesis of phospholipids containing hydroxylated fatty acids and have utilized this methodology to synthesize two naturally occurring hydroxylated lecithins (i.e. 1-palmitoyl-2-[15(S)-hydroxy-5E,8E,11E,13Z-eicosatetraenoyl]-sn-glycero-3-phosphocholine (1-palm-2-15HETE PC) and 1-palmitoyl-2-[5-hydroxy-6Z,8E,11E, 14E-eicosatetraenoyl]-sn-glycero-3-phosphocholine (1-palm-2-5HETE PC)). After protection of the hydroxylated fatty acid as its t-butyldimethylsilyl derivative, the anhydride of the protected fatty acid was formed utilizing dicyclohexylcarbodiimide and subsequently was condensed with a regiospecific lysolecithin utilizing pyrrolidinopyridine as catalyst to form the protected hydroxylated lecithin. Finally, hydroxylated lecithins were formed after removal of the t-butyldimethylsily group with acetic acid. Electron spin resonance spectroscopy was utilized to interrogate the molecular dynamics of lipid bilayers comprised of mixtures of the se hydroxylated lecithins and naturally occurring lecithins. Remarkably, the molecular dynamics of spin-labeled phospholipids in liposomes comprised of cholesterol and phosphatidylcholine were altered substantially after addition of only 3.5 mol% 1-palm-2-15HETE PC as assessed by the order parameter of 16-doxylstearoyl phosphatidylcholine.
AB - We have devised a general method for the synthesis of phospholipids containing hydroxylated fatty acids and have utilized this methodology to synthesize two naturally occurring hydroxylated lecithins (i.e. 1-palmitoyl-2-[15(S)-hydroxy-5E,8E,11E,13Z-eicosatetraenoyl]-sn-glycero-3-phosphocholine (1-palm-2-15HETE PC) and 1-palmitoyl-2-[5-hydroxy-6Z,8E,11E, 14E-eicosatetraenoyl]-sn-glycero-3-phosphocholine (1-palm-2-5HETE PC)). After protection of the hydroxylated fatty acid as its t-butyldimethylsilyl derivative, the anhydride of the protected fatty acid was formed utilizing dicyclohexylcarbodiimide and subsequently was condensed with a regiospecific lysolecithin utilizing pyrrolidinopyridine as catalyst to form the protected hydroxylated lecithin. Finally, hydroxylated lecithins were formed after removal of the t-butyldimethylsily group with acetic acid. Electron spin resonance spectroscopy was utilized to interrogate the molecular dynamics of lipid bilayers comprised of mixtures of the se hydroxylated lecithins and naturally occurring lecithins. Remarkably, the molecular dynamics of spin-labeled phospholipids in liposomes comprised of cholesterol and phosphatidylcholine were altered substantially after addition of only 3.5 mol% 1-palm-2-15HETE PC as assessed by the order parameter of 16-doxylstearoyl phosphatidylcholine.
KW - 15-hydroxyeicosatetraenoic acid
KW - 5-hydroxyeicosatetraenoic acid
KW - electron spin resonance
KW - phospholipids
UR - http://www.scopus.com/inward/record.url?scp=0025016946&partnerID=8YFLogxK
U2 - 10.1016/0009-3084(90)90117-A
DO - 10.1016/0009-3084(90)90117-A
M3 - Article
C2 - 2160333
AN - SCOPUS:0025016946
SN - 0009-3084
VL - 52
SP - 217
EP - 226
JO - Chemistry and Physics of Lipids
JF - Chemistry and Physics of Lipids
IS - 3-4
ER -