Synthesis of a new phosphoglycolipid with biological activity towards platelets.
Various synthetic as well as naturally occurring compounds have been found to exhibit platelet-activating factor (PAF)-like activity or to act as specific PAF inhibitors. In this work we have synthesized a new phosphoglycolipid, methyl 2,3,4-tri-O-acetyl-6-(1'-O-stearoyl-2'-O- acetyl-DL-glycero-3'-phosphoryl)-alpha-D-glucopyranoside ammonium salt, using a combination of known synthetic steps. This phosphoglycolipid was first purified on TLC (Rf 0.7, using chloroform/methanol/water, 65:25:4, v/v/v as solvent system). It was further purified onto a high performance liquid chromatography silica column with an elution system that contained acetonitrile and methanol (retention time 13.5 min). Its identification was based on chemical determinations and electrospray mass spectrometry analysis. The above compound induced washed platelet aggregation with an EC50 value at 2 x 10(-4) M. The aggregation curve was biphasic, the first wave of which was through the PAF way while the second one was through the ADP way. Treatment with acetylhydrolase resulted in a rapid decrease of the first wave of aggregation and in a slow decrease of the second wave. In lower concentrations, the phosphoglycolipid inhibited PAF- and thrombin-induced aggregation with IC50 values of the order of 10(-7) M. In conclusion, this phosphoglycolipid has a diverse biological activity. The PAF-like activity of this new lipid enforces the conception that PAF is a member of a large family consisting of lipid mediators.
Avramopoulou
V
V
Department of Chemistry, University of Athens, Greece.
Antonopoulou
S
S
Argyropoulos
D
D
Froussios
C
C
Demopoulos
C A
CA
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004224:Diterpenes; D005343:Fibrinolytic Agents / Q000494:pharmacology; D046934:Ginkgolides; D005960:Glucosides / Q000138:chemical synthesis / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology; D013058:Mass Spectrometry; D010712:Phosphatidic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D010944:Plants / Q000737:chemistry*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits
D018927:Anti-Asthmatic Agents; D004224:Diterpenes; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D005960:Glucosides; D007783:Lactones; D010712:Phosphatidic Acids; D010972:Platelet Activating Factor; C108067:methyl 2,3,4-tri-O-acetyl-6-(1'-O-stearoyl-2'-O-acetyl-DL-glycero-3'-phosphoryl)-alpha-D-glucopyranoside ammonium salt; C045856:ginkgolide B