Synthesis of lipidic amino acid and dipeptide inhibitors of human platelet phospholipase A2.
Phospholipases A2 (PLA2s) catalyze the hydrolysis of glycerophospholipids at the sn-2 position, and their inhibition is considered a rational approach for the prevention and treatment of inflammation. A number of amides and esters of alpha-amino acids with saturated linear side chains, esters of alpha-amino alcohols and derivatives of lipidic peptides were prepared and tested against secreted humal platelet phospholipase A2. Among the compounds tested the amides of free amino acids with long-chain amines presented the highest in vitro inhibitory activity.
Kokotos
G
G
Department of Chemistry, University of Athens, Greece.
Constantinou-Kokotou
V
V
Noula
C
C
Nicolaou
A
A
Gibbons
W A
WA
D000596:Amino Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010712:Phosphatidic Acids / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000596:Amino Acids; D004151:Dipeptides; D004791:Enzyme Inhibitors; D010712:Phosphatidic Acids; D010741:Phospholipases A; D054467:Phospholipases A2