Abstract
Within recent years, ganglioside patterns have been increasingly analyzed by MS. However, internal standards for calibration are only available for gangliosides GM1, GM2, and GM3. For this reason, we prepared homologous internal standards bearing nonnatural fatty acids of the major mammalian brain gangliosides GM1, GD1a, GD1b, GT1b, and GQ1b, and of the tumor-associated gangliosides GM2 and GD2. The fatty acid moieties were incorporated after selective chemical or enzymatic deacylation of bovine brain gangliosides. For modification of the sphingoid bases, we developed a new synthetic method based on olefin cross metathesis. This method was used for the preparation of a lyso-GM1 and a lyso-GM2 standard. The total yield of this method was 8.7% for the synthesis of d17:1-lyso-GM1 from d20:1/18:0-GM1 in four steps. The title compounds are currently used as calibration substances for MS quantification and are also suitable for functional studies.
Highlights
Within recent years, ganglioside patterns have been increasingly analyzed by MS
The ganglioside classes were purified by normal phase (NP) column chromatography using different techniques and different solvent systems
Development of a new synthetic method to modify the sphingosine chain of gangliosides We developed a synthetic method based on the olefin cross metathesis for the preparation of gangliosides and lysogangliosides with homogenous and, if required, artificial sphingoid bases
Summary
Internal standards for calibration are only available for gangliosides GM1, GM2, and GM3 For this reason, we prepared homologous internal standards bearing nonnatural fatty acids of the major mammalian brain gangliosides GM1, GD1a, GD1b, GT1b, and GQ1b, and of the tumor-associated gangliosides GM2 and GD2. The main gangliosides in adult mammalian brain are GM1 (Fig. 1), GD1a, GD1b, GT1b, 9-O-Ac-GT1b, and GQ1b (4). They contain mostly C18- and C20-sphingosine acylated with stearic acid, which constitutes more than 80% of the total ganglioside fatty acid content in the nervous system (4). The majority of gangliosides are localized in the outer leaflet of the plasma membrane They are anchored to the membrane by their hydrophobic ceramide part, while their hydrophilic carbohydrate part extrudes into the extracellular space. Elevated levels of lyso-GM2 and lyso-GA2 are present in the brains of patients with GM2 gangliosidoses (21), and elevated levels of lyso-GM1 and lyso-GA1 are present in patients with GM1
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