Design and Synthesis of Highly Potent and Plasma-Stable Dimeric Inhibitors of the PSD-95-NMDA Receptor Interaction

被引：53

作者：

Bach, Anders ^{[1
]}

Chi, Celestine N. ^{[2
]}

Pang, Gar F. ^{[1
]}

Olsen, Lars ^{[1
]}

Kristensen, Anders S. ^{[1
]}

Jemth, Per ^{[2
]}

Stromgaard, Kristian ^{[1
]}

机构：

[1] Univ Copenhagen, Dept Med Chem, DK-2100 Copenhagen, Denmark

[2] Uppsala Univ, Dept Med Biochem & Microbiol, S-75123 Uppsala, Sweden

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2009年 / 48卷 / 51期

基金：

瑞典研究理事会;

关键词：

bridging ligands; dimerization; inhibitors; protein-protein interactions; receptors; PDZ DOMAIN PROTEINS; FLEXIBLE LINKERS; BINDING; LIGAND; AFFINITY; ANTAGONISTS; PEPTIDES; TARGETS; STROKE;

D O I：

10.1002/anie.200904741

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

On the double: Dimerization of monomeric peptide ligands towards the PDZ domains of the protein PSD-95 (postsynaptic density 95) leads to potent inhibitors of protein-protein interactions with stability in blood plasma. Optimization of the length of the polyethylene glycol linker results in unprecedented affinity for inhibitors of the PDZ1-2 domain (see picture). © 2009 Wiley-VCH Verlag GmbH &. Co. KGaA.

引用

页码：9685 / 9689

页数：5

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