A novel molecular design of thrombin receptor antagonist

T Fujita; M Nakajima; Y Inoue; T Nose; Y Shimohigashi

doi:10.1016/s0960-894x(99)00202-4

A novel molecular design of thrombin receptor antagonist

Bioorg Med Chem Lett. 1999 May 17;9(10):1351-6. doi: 10.1016/s0960-894x(99)00202-4.

Authors

T Fujita¹, M Nakajima, Y Inoue, T Nose, Y Shimohigashi

Affiliation

¹ Department of Molecular Chemistry, Graduate School of Science, Kyushu University, Fukuoka, Japan.

PMID: 10360734
DOI: 10.1016/s0960-894x(99)00202-4

Abstract

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.

MeSH terms

Antithrombins / chemical synthesis
Antithrombins / chemistry*
Antithrombins / metabolism
Binding Sites
Computer Simulation
Drug Design
Humans
Lysine / metabolism
Models, Molecular
Platelet Aggregation Inhibitors / chemical synthesis
Platelet Aggregation Inhibitors / chemistry
Platelet Aggregation Inhibitors / metabolism
Receptors, Thrombin / antagonists & inhibitors*
Receptors, Thrombin / chemistry
Receptors, Thrombin / metabolism
Static Electricity
Structure-Activity Relationship

Substances

Antithrombins
Platelet Aggregation Inhibitors
Receptors, Thrombin
Lysine