A novel molecular design of thrombin receptor antagonist.
In a computer modeling of transmembrane domains of human thrombin receptor, Lys-158 was found near the ligand binding site. To capture this basic residue, analogs of peptide ligand containing a series of acidic amino acids were synthesized and assayed for human platelet aggregation, and Ser-(p-F)Phe-Aad(= alphaaminoadipic acid)-Leu-Arg-Asn-Pro-NH2 was found to be a potent antagonist.
Fujita
T
T
Department of Molecular Chemistry, Graduate School of Science, Kyushu University, Fukuoka, Japan.
Nakajima
M
M
Inoue
Y
Y
Nose
T
T
Shimohigashi
Y
Y
D000991:Antithrombins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008958:Models, Molecular; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship
D000991:Antithrombins; D010975:Platelet Aggregation Inhibitors; D018179:Receptors, Thrombin; D008239:Lysine