Robust Generation of Lead Compounds for Protein-Protein Interactions by Computational and MCR Chemistry: p53/Hdm2 Antagonists

被引：118

作者：

Czarna, Anna ^{[3
]}

Beck, Barbara ^{[1
,2
]}

Srivastava, Stuti ^{[1
,2
]}

Popowicz, Grzegorz M. ^{[3
]}

Wolf, Siglinde ^{[3
]}

Huang, Yijun ^{[1
,2
]}

Bista, Michal ^{[3
]}

Holak, Tad A. ^{[3
]}

Doemling, Alexander ^{[1
,2
]}

机构：

[1] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA

[2] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15261 USA

[3] Max Planck Inst Biochem, D-82152 Martinsried, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2010年 / 49卷 / 31期

关键词：

antagonists; drug discovery; multicomponent reactions; p53/Hdm2; interaction; protein-protein interactions; DRUG DISCOVERY; FORCE-FIELD; HOT-SPOTS; MDM2; NMR; POTENT; P53; INHIBITORS; DESIGN; ASSAY;

D O I：

10.1002/anie.201001343

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

The parallel discovery of multiple scaffolds useful to antagonize the cancer-relevant proteinprotein interaction p53/Hdm2 is described. The new method is based on the tightly interwoven interplay of multicomponent reaction chemistry, structural biology, computational chemistry, and high-content NMR-based screening. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：5352 / 5356

页数：5

共 40 条

[1]

New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays [J].

Baell, Jonathan B. ;

Holloway, Georgina A. .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (07) :2719-2740

[2]

Betti M., 1900, GAZZ CHIM ITAL, V30, P306

[3]

Robust NMR Screening for Lead Compounds Using Tryptophan-Containing Proteins [J].

Bista, Michal ;

Kowalska, Kaja ;

Janczyk, Weronika ;

Doemling, Alexander ;

Holak, Tad A. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (22) :7500-+

[4]

Anatomy of hot spots in protein interfaces [J].

Bogan, AA ;

Thorn, KS .

JOURNAL OF MOLECULAR BIOLOGY, 1998, 280 (01) :1-9

[5]

Efficient C2 functionalisation of 2H-2-imidazolines [J].

Bon, Robin S. ;

Sprenkels, Nanda E. ;

Koningstein, Manoe M. ;

Schmitz, Rob F. ;

de Kanter, Frans J. J. ;

Doemling, Alexander ;

Groen, Marinus B. ;

Orru, Romano V. A. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2008, 6 (01) :130-137

[6]

Novel multicomponent reaction for the combinatorial synthesis of 2-imidazolines [J].

Bon, RS ;

Hong, CG ;

Bouma, MJ ;

Schmitz, RF ;

de Kanter, FJJ ;

Lutz, M ;

Spek, AL ;

Orru, RVA .

ORGANIC LETTERS, 2003, 5 (20) :3759-3762

[7]

STUDIES ON ISOCYANIDES - SYNTHESIS OF N-TOSYLGUANIDINES [J].

BOSSIO, R ;

MARCACCINI, S ;

PEPINO, R .

TETRAHEDRON LETTERS, 1995, 36 (13) :2325-2326

[8]

High affinity interaction of the p53 peptide-analogue with human Mdm2 and Mdmx [J].

Czarna, Anna ;

Popowicz, Grzegorz M. ;

Pecak, Aleksandra ;

Wolf, Siglinde ;

Dubin, Grzegorz ;

Holak, Tad A. .

CELL CYCLE, 2009, 8 (08) :1176-1184

[9]

Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction [J].

Ding, Ke ;

Lu, Yipin ;

Nikolovska-Coleska, Zaneta ;

Wang, Guoping ;

Qiu, Su ;

Shangary, Sanjeev ;

Gao, Wei ;

Qin, Dongguang ;

Stuckey, Jeanne ;

Krajewski, Krzysztof ;

Roller, Peter P. ;

Wang, Shaomeng .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (12) :3432-3435

[10]

Recent developments in isocyanide based multicomponent reactions in applied chemistry [J].

Dömling, A .

CHEMICAL REVIEWS, 2006, 106 (01) :17-89

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