Inhibitors of lipid phosphatidate receptors: N-palmitoyl-serine and N-palmitoyl-tyrosine phosphoric acids.
An improved synthesis of two lipid phosphoric acids, N-palmitoyl-L-serine phosphoric acid (NP-Ser-PA) and N-palmitoyl-L-tyrosine phosphoric acid (NP-Tyr-PA), from the benzyl esters of L-serine and L-tyrosine is described. The sequence of N-acylation, followed by phosphitylation with N, N-diisopropyl dibenzyl phosphoramidite, oxidation to the corresponding phosphate triesters, and simultaneous debenzylation of the dibenzyl phosphate and benzyl carboxylic esters gave NP-Ser-PA and NP-Tyr-PA in high overall yields. NP-Ser-PA and NP-Tyr-PA and their D stereoisomers were potent reversible inhibitors of the lysophosphatidic acid receptors expressed in Xenopus oocytes, thus providing prototypic structures for the development of inhibitors of the lysophosphatidate family of phospholipid growth factors.
Bittman
R
R
Department of Chemistry and Biochemistry, Queens College, City University of New York, Flushing 11367-1597, USA.
Swords
B
B
Liliom
K
K
Tigyi
G
G
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D004553:Electric Conductivity; D005260:Female; D009865:Oocytes / Q000378:metabolism / Q000648:ultrastructure; D010168:Palmitates / Q000138:chemical synthesis* / Q000494:pharmacology; D010768:Phosphoserine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D019000:Phosphotyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D014981:Xenopus
D018118:Chloride Channels; C101516:N-palmitoylserine phosphoric acid; C101517:N-palmitoyltyrosine phosphoric acid; D010168:Palmitates; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D011994:Recombinant Proteins; D010768:Phosphoserine; D019000:Phosphotyrosine