Modulators of 14-3-3 Protein-Protein Interactions

被引：211

作者：

Stevers, Loes M. ^{[1
,2
]}

Sijbesma, Eline ^{[1
,2
]}

Botta, Maurizio ^{[3
]}

MacKintosh, Carol ^{[4
]}

Obsil, Tomas ^{[5
]}

Landrieu, Isabelle ^{[6
]}

Cau, Ylenia ^{[3
]}

Wilson, Andrew J. ^{[7
,8
]}

Karawajczyk, Anna ^{[9
]}

Eickhoff, Jan ^{[10
]}

Davis, Jeremy ^{[11
]}

Hann, Michael ^{[12
]}

O'Mahony, Gavin ^{[13
]}

Doveston, Richard G. ^{[1
,2
]}

Brunsveld, Luc ^{[1
,2
]}

Ottmann, Christian ^{[1
,2
,14
]}

机构：

[1] Eindhoven Univ Technol, Biol Chem Lab, Dept Biomed Engn, POB 513, NL-5600 MB Eindhoven, Netherlands

[2] Eindhoven Univ Technol, ICMS, POB 513, NL-5600 MB Eindhoven, Netherlands

[3] Univ Siena, Dept Biotechnol Chem & Pharm, Via Aldo Moro 2, I-53100 Siena, Italy

[4] Univ Dundee, Div Cell & Dev Biol, Sch Life Sci, Dundee DD1 4HN, Scotland

[5] Charles Univ Prague, Fac Sci, Dept Phys & Macromol Chem, CR-11636 Prague, Czech Republic

[6] Univ Lille, CNRS, UMR 8576, F-59000 Lille, France

[7] Univ Leeds, Sch Chem, Woodhouse Lane, Leeds LS2 9JT, W Yorkshire, England

[8] Univ Leeds, Astbury Ctr Struct Mol Biol, Woodhouse Lane, Leeds LS2 9JT, W Yorkshire, England

[9] Taros Chem GmbH & Co KG, D-44227 Dortmund, Germany

[10] Lead Discovery Ctr GmbH, D-44227 Dortmund, Germany

[11] UCB Celltech, 216 Bath Rd, Slough SL1 3WE, Berks, England

[12] GlaxoSmithKline, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England

[13] AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev Biotech Unit, Pepparedsleden 1, SE-43183 Molndal, Sweden

[14] Univ Duisburg Essen, Dept Chem, Univ Str 7, D-45141 Essen, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 61卷 / 09期

关键词：

MEMBRANE H+-ATPASE; ELEMENT-BINDING PROTEIN; SMALL-MOLECULE STABILIZATION; PROTON PUMP ATPASE; HEAT-SHOCK-PROTEIN; DRUG DISCOVERY; STRUCTURAL-CHARACTERIZATION; TOXOPLASMA-GONDII; ECHINOCOCCUS-MULTILOCULARIS; ENANTIOSELECTIVE SYNTHESIS;

D O I：

10.1021/acs.jmedchem.7b00574

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Direct interactions between proteins are essential for the regulation of their functions in biological pathways. Targeting the complex network of protein protein interactions (PPIs) has now been widely recognized as an attractive means to therapeutically intervene in disease states. Even though this is a challenging endeavor and PPIs have long been regarded as "undruggable" targets, the last two decades have seen an increasing number of successful examples of PPI modulators, resulting in growing interest in this field. PPI modulation requires novel approaches and the integrated efforts of multiple disciplines to be a fruitful strategy. This perspective focuses on the hub-protein 14-3-3, which has several hundred identified protein interaction partners, and is therefore involved in a wide range of cellular processes and diseases. Here, we aim to provide an integrated overview of the approaches explored for the modulation of 14-3-3 PPIs and review the examples resulting from these efforts in both inhibiting and stabilizing specific 14-3-3 protein complexes by small molecules, peptide mimetics, and natural products.

引用

页码：3755 / 3778

页数：24

共 164 条

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