Effect of the structure of adenosine mimic of bisubstrate-analog inhibitors on their activity towards basophilic protein kinases

被引：13

作者：

Enkvist, Erki ^{[1
]}

Kriisa, Marie ^{[1
]}

Roben, Mart ^{[1
]}

Kadak, Grete ^{[1
]}

Raidaru, Gerda ^{[1
]}

Uri, Asko ^{[1
]}

机构：

[1] Univ Tartu, Inst Chem, EE-51014 Tartu, Estonia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 21期

关键词：

Protein kinases; AGC kinases; PKA; PKB/Akt; ROCK; Bisubstrate inhibitors; Oligoarginine; PEPTIDE INHIBITORS; DISCOVERY; DESIGN; AKT;

D O I：

10.1016/j.bmcl.2009.09.026

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Previously reported structural fragments that associate with the ATP-binding pocket of basophilic protein kinases were conjugated with D-arginine-containing peptides. Inhibitory potency of the resulting bisubstrate-analog inhibitors towards PKA and ROCK-II extended to subnanomolar range. The conjugates incorporating 2-pyrimidyl-5-amidothiophene fragment had the highest activity and at 100 nM concentration exhibited over 80% inhibition of most of the tested basophilic kinases of the AGC group. (C) 2009 Elsevier Ltd. All rights reserved.

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收藏

页码：6098 / 6101

页数：4

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