Substituted 1,4-benzodiazepine-2,5-diones as alpha-helix mimetic antagonists of the HDM2-p53 protein-protein interaction.
作者： Maxwell D. Cummings , Carsten Schubert , Daniel J. Parks , Raul R. Calvo , Louis V. LaFrance
DOI: 10.1111/J.1747-0285.2006.00365.X
关键词:
摘要: Small molecule antagonists of protein–protein interactions represent a particular challenge for pharmaceutical discovery. One approach to finding molecules that can disrupt these is seek mimics common protein structure motifs. We present an analysis how based on the 1,4-benzodiazepine-2,5-dione scaffold serve mimic side-chains presented by hydrophobic face two turns α-helix derived from tumor suppressor p53, and thus antagonize HDM2-p53 binding interaction.
sci-hub.se 参考文章(38)
Chène P, Howard Sf, Lane Dp, Picksley Sm, Böttger, Hochkeppel Hk, Garcia-Echeverria C, Böttger A, Identification of novel mdm2 binding peptides by phage display. Oncogene. ,vol. 13, pp. 2141- 2147 ,(1996)
Peter S. Galatin, Donald J. Abraham, A Nonpeptidic Sulfonamide Inhibits the p53−mdm2 Interaction and Activates p53-Dependent Transcription in mdm2-Overexpressing Cells Journal of Medicinal Chemistry. ,vol. 47, pp. 4163- 4165 ,(2004) , 10.1021/JM034182U
Paul H. Kussie, Svetlana Gorina, Vincent Marechal, Brian Elenbaas, Jacque Moreau, Arnold J. Levine, Nikola P. Pavletich, Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science. ,vol. 274, pp. 948- 953 ,(1996) , 10.1126/SCIENCE.274.5289.948
W.C. Ripka, G.V. De Lucca, A.C. Bach, R.S. Pottorf, J.M. Blaney, Protein β-turn mimetics II: Design, synthesis, and evaluation in the cyclic peptide gramicidin S Tetrahedron. ,vol. 49, pp. 3609- 3628 ,(1993) , 10.1016/S0040-4020(01)90218-2
Christos Papageorgiou, Xaver Borer, A non-peptide ligand for the somatostatin receptor having a benzodiazepinone structure Bioorganic & Medicinal Chemistry Letters. ,vol. 6, pp. 267- 272 ,(1996) , 10.1016/0960-894X(96)00003-0
Matthew G. Bursavich, Daniel H. Rich, Designing non-peptide peptidomimetics in the 21st century: inhibitors targeting conformational ensembles. Journal of Medicinal Chemistry. ,vol. 45, pp. 541- 558 ,(2002) , 10.1021/JM010425B
Brendan P. Orner, Justin T. Ernst, Andrew D. Hamilton, Toward Proteomimetics: Terphenyl Derivatives as Structural and Functional Mimics of Extended Regions of an α-Helix Journal of the American Chemical Society. ,vol. 123, pp. 5382- 5383 ,(2001) , 10.1021/JA0025548
Thorsten Berg, Modulation of Protein–Protein Interactions with Small Organic Molecules Angewandte Chemie International Edition. ,vol. 42, pp. 2462- 2481 ,(2003) , 10.1002/ANIE.200200558
Carol Prives, SIGNALING TO P53 : BREAKING THE MDM2-P53 CIRCUIT Cell. ,vol. 95, pp. 5- 8 ,(1998) , 10.1016/S0092-8674(00)81774-2
Olaf Kutzki, Hyung Soon Park, Justin T Ernst, Brendan P Orner, Hang Yin, Andrew D Hamilton, None, Development of a Potent Bcl-xL Antagonist Based on α-Helix Mimicry Journal of the American Chemical Society. ,vol. 124, pp. 11838- 11839 ,(2002) , 10.1021/JA026861K