Synthesis of plasmalopsychosines A and B, two novel lysosphingolipids found in human brain

Sadozai, Khalid K.; Anand, Jasbir K.; Nudelman, Edward; Hakomori, Sen‐itiroh

doi:10.1016/0008-6215(93)80120-4

Cited by 6 publications

(9 citation statements)

References 21 publications

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“…Proton chemical shifts are reported relative to 3-(trimethylsilyl)propionic acid, 2,2,3,3-d 4 sodium salt (Aldrich, Milwaukee, WI) used as an external standard. The proton resonances were assigned using the double-quantum filtered correlated spectroscopy spectrum and by comparison with the reported assignments for psychosine and related galactocerebrosides (17,18).…”

Section: Methodsmentioning

confidence: 99%

Physicochemical characterization of psychosine by ¹H nuclear magnetic resonance and electron microscopy

Őrfi

Larive

Levine

1997

Lipids

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Krabbe's disease is an autosomal recessive disease that affects the lysosomal enzyme galactosylceramidase. The storage of one of its substrates, psychosine (beta-galactosyl-sphingosine), is thought to be responsible for the induction of pathological changes. Psychosine has a free amine group which is necessary for the mediation of its toxic effects. In the present study, the physicochemical properties of psychosine were investigated. Nuclear magnetic resonance (NMR) detected pH titration was used to determine that the amine group had a pKa of 7.18 +/- 0.05. Pulsed-field gradient NMR spectroscopy was used to determine that the diffusion coefficient of 2.8 mM psychosine in D2O at pD 4.46 or 7.04 is 1.16 +/- 0.02 x 10(-10) m2/s or 0.77 +/- 0.02 x 10(-10) m2/s, respectively. Negative staining electron microscopy (EM) studies of acidic and neutral solutions of psychosine also were performed. At pH 4.5, spherical structures were formed, which were relatively stable between 3, 120, and 216 h following preparation; the diameter ranged from approximately 14 nm at the earliest time point to approximately 18 nm at the last time point. The critical micelle concentration (CMC) was 1.26 mM at pH 4.0. At pH 7.1, the structures changed from spherical structures with a diameter of 15-23 nm, at the earliest time point, to a heterogeneous population of structures ranging from spherical structures, with a diameter of only a few nm, to irregularly shaped oblong structures that had one or more dimensions exceeding 100 nm. The NMR and EM data indicate that the deprotonation of the amine group causes psychosine to form aggregates that are unstable, which prevents a determination of the CMC at a neutral pH. These data indicate that molecular interactions of psychosine at the acidic pH of the lysosome, where it is normally digested, are more orderly than those at the pH of the cytoplasm or extracellular space where psychosine goes during disease.

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Section: Methodsmentioning

confidence: 99%

Physicochemical characterization of psychosine by ¹H nuclear magnetic resonance and electron microscopy

Őrfi

Larive

Levine

1997

Lipids

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“…Their chemical structures, including the presence and chain length of the fatty aldehyde, were characterized mainly with mass spectra using fast-atom bombardment-mass spectrometry (FAB-MS), and by methylation analysis followed by analysis by gas chromatography-mass spectrometry (GC-MS). Furthermore, isomers of plasmalopsychosine have been chemically synthesized from psychosine by acetalization, confirming the isomeric structure of the acetal group to be identical to that of naturally occurring plasmalolipid (11). The isomeric stereostructure of natural plasmaloGalCer from equine brain, which can have two isomers with different directions of the fatty acetal chain, endo -and exotypes, was characterized as the former type by proton nuclear magnetic resonance spectroscopy (NMR) by us, after chemical synthesis of the plasmalolipid (12).…”

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confidence: 69%

Novel plasmalogalactosylalkylglycerol from equine brain

Yachida

Kashiwagi

Mikami

et al. 1999

Journal of Lipid Research

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A novel galactosylalkylglycerol modified with a long-chain cyclic acetal at the sugar moiety, 3-O -(4 6 -plasmalogalactosyl) 1-O -alkylglycerol, was isolated from equine brain. The presence of cyclic acetal linkage, its linked position, and the length of the acetal chain of the natural plasmalo lipid were determined by proton NMR spectroscopy and fast-atom bombardment-mass spectrometry, as well as gas chromatography-mass spectrometry and gas-liquid chromatography. To identify the isomeric stereostructure of the natural product, the plasmalo derivative was chemically synthesized from 3-O -galactosyl 2-O -acyl 1-O -alkyl glyceride through acetalization after deacylation. As a result, the direction and position of the acetal chain of the natural plasmalo lipid were characterized as an " endo "-type 4 ,6 -Oacetal derivative linked to galactoside by comparison with the NMR data of the synthesized product. The chain lengths of alkyl and acetal groups were C 14 for the former and C 16 and C 18 for the latter, and those for the latter group were mostly similar to those of plasmalogalactosyl ceramide, which was previously isolated from equine brain. -Yachida,

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“…The H2 multiplet of the long-chain base (L-H2), however, resonated in a much higher field (ϳ1 ppm higher) than that in GalCer (21), indicating that an amino group at the C2 position is not acylated (22,23). A triplet at 4.48 ppm (P-H1), coupled with a methylene signal at 1.49 ppm (P-H2), was assigned to an acetal proton (-O-CH(-O)-CH 2 -) (24). A triplet at 5.32 ppm, attributed to allylic protons, shows the presence of a substantial amount of cis-double bond in the fatty aldehyde.…”

Section: Hydrolysis Of Px and Plps And Methylation Analysis Bymentioning

confidence: 95%

A Novel Plasmal Conjugate to Glycerol and Psychosine (“Glyceroplasmalopsychosine”)

Hikita

Tadano-Aritomi

Iida-Tanaka

et al. 2001

Journal of Biological Chemistry

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A novel plasmal conjugate of glycosphingolipid having cationic lipid properties was isolated from the white matter of bovine brain. Linkage analysis of galactosyl residue by methylation, liquid secondary ion, and electrospray ionization mass spectrometry of intact and methylated derivatives, and by 1 H-and 13 C-NMR spectroscopy, identified the structure unambiguously as an O-acetal conjugate of plasmal to the primary hydroxyl group of glycerol and to the 6-hydroxyl group of galactosyl residue of ␤-galactosyl 131 sphingosine (psychosine). This novel compound is hereby termed "glyceroplasmalopsychosine"; its structure is shown below.Long chain aldehydes, hexadecanal and octadecanal, with or without an olefinic double bond, are collectively called plasmal, and are known as a common component of two classes of lipid conjugates, described as follows: (i) the classically well-established phospholipid plasmalogen (1, 2), in which plasmal is conjugated as O-alk-1-enyl (vinyl ether) group to one of the hydroxyl groups of glycerol in phosphatidylethanolamine or phosphatidylcholine 1 ; (ii) the recently found novel type of glycosphingolipid (GSL) 2 in which a plasmal is conjugated to two hydroxyl groups of the galactosyl residue of galactosylsphingosine (psychosine) or galactosylceramide through cyclic acetal linkage; these were originally isolated from human brain white matter and are termed, respectively, plasmalopsychosine (PLPS) and plasmalocerebroside. Depending on the position of hydroxyl group involved in acetal linkages, 3,4-and 4,6-cyclic plasmal conjugates of PLPS and plasmalocerebroside are termed, respectively, PLPS A or B (3), and plasmalocerebroside A or B (4). More recently, a GSL having the same structure as plasmalocerebroside B (4,6-cyclic acetal) was isolated from equine brain. The orientation of the acetal chain linked to galactosyl residue through asymmetric carbon 1 of plasmal was identified as "endo" type, initially on model plasmal conjugate of methyl-␤-galactoside (45), subsequently on 4,6-plasmalocerebroside (5). A similar 4,6-cyclic acetal conjugate of plasmal to galactosyl alkylglyceride was isolated and characterized (6). All these conjugates are characterized by typical aldehyde reaction (e.g. oxidizing Schiff's reagent to give red color, after brief acid treatment). Among them, only PLPS shows cationic properties, and can be isolated by cation-exchange chromatography on carboxymethyl (CM)-Sephadex column in organic solvent, because of its free amino group at Sph residue. Cationic lipids are rare in animal cells and tissues (see "Discussion"). PLPS has the novel effect of inducing signal transduction in neuronal cells, particularly neuritogenesis in PC12 cells without addition of nerve growth factor; i.e. PLPS mimics the effect of nerve growth factor (7). During previous studies, we noticed the presence of cationic lipids having slower TLC migration rate than PLPS in human brain (3). We therefore undertook further systematic study of cationic lipids with plasmal conjugate in bovine brain.Durin...

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Synthesis of plasmalopsychosines A and B, two novel lysosphingolipids found in human brain

Cited by 6 publications

References 21 publications

Physicochemical characterization of psychosine by ¹H nuclear magnetic resonance and electron microscopy

Physicochemical characterization of psychosine by ¹H nuclear magnetic resonance and electron microscopy

Novel plasmalogalactosylalkylglycerol from equine brain

A Novel Plasmal Conjugate to Glycerol and Psychosine (“Glyceroplasmalopsychosine”)

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Synthesis of plasmalopsychosines A and B, two novel lysosphingolipids found in human brain

Cited by 6 publications

References 21 publications

Physicochemical characterization of psychosine by 1H nuclear magnetic resonance and electron microscopy

Physicochemical characterization of psychosine by 1H nuclear magnetic resonance and electron microscopy

Novel plasmalogalactosylalkylglycerol from equine brain

A Novel Plasmal Conjugate to Glycerol and Psychosine (“Glyceroplasmalopsychosine”)

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Physicochemical characterization of psychosine by ¹H nuclear magnetic resonance and electron microscopy

Physicochemical characterization of psychosine by ¹H nuclear magnetic resonance and electron microscopy