Selective Identification of Cooperatively Binding Fragments in a High-Throughput Ligation Assay Enables Development of a Picomolar Caspase-3 Inhibitor

被引：40

作者：

Schmidt, Marco F. ^{[1
,2
]}

El-Dahshan, Adeeb ^{[1
,2
]}

Keller, Sandro ^{[1
]}

Rademann, Joerg ^{[1
,2
]}

机构：

[1] Leibniz Inst Mol Pharmacol FMP, D-13125 Berlin, Germany

[2] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2009年 / 48卷 / 34期

关键词：

caspase-3; drug discovery; fluorescence polarization; high-throughput screening; protease inhibitors; DYNAMIC COMBINATORIAL CHEMISTRY; DRUG DISCOVERY; LEAD DISCOVERY; APOPTOSIS; POTENT; CRYSTALLOGRAPHY; PROTEINS; LIGANDS; DESIGN;

D O I：

10.1002/anie.200901647

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Putting the pieces together: A chemically reactive fluorescence polarization (FP) probe can be use to detect positively cooperative fragments through the overadditive binding of their ligation products. For confirmation, an stable derivative of the ligation product was prepared and found to be significantly more active than all previously reported caspase-3 inhibitors. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：6346 / 6349

页数：4

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