Structure-activity relationships of RGD mimetics as fibrinogen-receptor antagonists.
The activities of a series of RGD mimetics, which contained a variety of cationic structures, for the inhibition of platelet aggregation and fibrinogen-receptor binding were measured. The stability of the coulombic ion-pairing complex of the model compounds with the acetate anion as a model for the receptor was calculated in terms of the ionic interaction energy. The results suggest that stability is one of the significant factors which govern the inhibitory potency of fibrinogen-receptor binding. The distance between cationic and anionic groups might also affect the potency. A compound which contained an amidinophenyl structure as the cationic moiety showed exceptionally high inhibitory activity, suggesting that some other factors, in addition to coulombic interaction and the distance, affect the potency.
Miyashita
M
M
Graduate School of Agriculture, Kyoto University, Japan.
Akamatsu
M
M
Ueno
H
H
Nakagawa
Y
Y
Nishimura
K
K
Hayashi
Y
Y
Sato
Y
Y
Ueno
T
T
D001792:Blood Platelets / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D005343:Fibrinolytic Agents; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen