DEVELOPMENT OF A POTENT THROMBIN RECEPTOR-LIGAND

被引：67

作者：

FENG, DM ^{[1
]}

VEBER, DF ^{[1
]}

CONNOLLY, TM ^{[1
]}

CONDRA, C ^{[1
]}

TANG, MJ ^{[1
]}

NUTT, RF ^{[1
]}

机构：

[1] MERCK SHARP & DOHME RES LABS,DEPT BIOL CHEM,W POINT,PA 19486

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 20期

关键词：

D O I：

10.1021/jm00020a029

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The N-terminal thrombin receptor peptide H-Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe-OH (1) fully activates the thrombin receptor with an EC(50) Of 10 mu M Structural features in the tetradecapeptide which are responsible for receptor activation have been elucidated. Agonist potency has been enhanced 1000-fold with the design of the shortened peptide H-Ala-Phe(p-F)-Arg-Cha-HArg-Tyr-NH2 (56). This analog exhibits an EC(50) of 0.01 mu M and is the most potent agonist for receptor activation reported to date. The monoiodinated derivative H-Ala-Phe(p-F)-Arg-Cha-HArg-Tyr(3-I)-NH2 (59) exhibits an EC(50) of 0.03 mu M, a level sufficient for development of a radioligand.

引用

页码：4125 / 4130

页数：6

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