The structure-activity relationships of a series of suicide inhibitors of phospholipase A2.
A series of mechanism-based inhibitors of phospholipase A2 (SIBLINKS) were synthesized. These new SIBLINKS are phospholipid analogues that contain a para-substituted phenyl 3,3-dimethylglutaryl group in the place of the sn-2 acyl chain. The effect of the phenyl leaving group on inhibitory activity was studied by varying the electron-withdrawing ability of the para-substituted group. A strong correlation was observed between the leaving group potential of the suicide inhibitor and the inhibitory activity of the derivative toward cobra venom phospholipase A2.
Yu
L
L
La Jolla Pharmaceutical Co., San Diego, CA 92121, USA.
Ternansky
R J
RJ
Victoria
E J
EJ
Chang
J
J
Coutts
S M
SM
D000818:Animals; D015195:Drug Design; D004546:Elapid Venoms / Q000037:antagonists & inhibitors; D017815:Elapidae; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010743:Phospholipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004546:Elapid Venoms; D004791:Enzyme Inhibitors; D010636:Phenols; D010743:Phospholipids; D010741:Phospholipases A; D054467:Phospholipases A2