Phospholipids chiral at phosphorus. Synthesis and stereospecificity of phosphorothioate analogues of platelet-activating factor.
RP and SP isomers of 1-O-hexadecyl-2-acetyl-3-thiophosphocholine (AGEPsC) have been synthesized. The activity of these isomers in platelet aggregation and serotonin secretion was compared with that of 1-O-hexadecyl-2-acetyl-3-phosphocholine (AGEPC). The results show that (SP)-AGEPsC has the same activity as AGEPC within experimental error in both assays. The RP isomer, however, is only 0.6-2% as active as AGEPC in platelet aggregation and serotonin release. The results suggest that the phosphate group of AGEPC is likely to be involved in the interactions with its receptor, at least in the events leading to platelet aggregation and secretion.
Rosario-Jansen
T
T
Department of Chemistry, Ohio State University, Columbus 43210.
Jiang
R T
RT
Tsai
M D
MD
Hanahan
D J
DJ
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D012701:Serotonin / Q000097:blood; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D010972:Platelet Activating Factor; C057211:1-O-hexadecyl-2-acetyl-3-thiophosphocholine; D012701:Serotonin