Volume 5, Issue 10 p. 1701-1705
Communication

20S Proteasome Inhibition: Designing Noncovalent Linear Peptide Mimics of the Natural Product TMC-95A

Prof. Dr. Michael Groll

Prof. Dr. Michael Groll

Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching (Germany), Fax: (+49) 89-289-13363

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Nerea Gallastegui

Nerea Gallastegui

Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching (Germany), Fax: (+49) 89-289-13363

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Xavier Maréchal

Xavier Maréchal

Enzymologie Moléculaire et Fonctionnelle, UR4-UPMC, Case 256, 6 eme Étage A, 7 Quai St-Bernard 75252 Paris Cedex 05 (France), Fax: (+33) 144-27-5022

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Dr. Virginie Le Ravalec

Dr. Virginie Le Ravalec

Chimie et Photonique Moléculaires, Université de Rennes 1, CNRS UMR 6510, Bâtiment 10, Case 1012, Campus de Beaulieu, 35042 Rennes Cedex (France), Fax: (+33) 223-23-6955

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Dr. Nicolas Basse

Dr. Nicolas Basse

Enzymologie Moléculaire et Fonctionnelle, UR4-UPMC, Case 256, 6 eme Étage A, 7 Quai St-Bernard 75252 Paris Cedex 05 (France), Fax: (+33) 144-27-5022

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Dr. Nicolas Richy

Dr. Nicolas Richy

Chimie et Photonique Moléculaires, Université de Rennes 1, CNRS UMR 6510, Bâtiment 10, Case 1012, Campus de Beaulieu, 35042 Rennes Cedex (France), Fax: (+33) 223-23-6955

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Dr. Emilie Genin

Dr. Emilie Genin

Chimie et Photonique Moléculaires, Université de Rennes 1, CNRS UMR 6510, Bâtiment 10, Case 1012, Campus de Beaulieu, 35042 Rennes Cedex (France), Fax: (+33) 223-23-6955

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Prof. Dr. Robert Huber

Prof. Dr. Robert Huber

Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, 82152 Martinsried (Germany)

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Prof. Dr. Luis Moroder

Prof. Dr. Luis Moroder

Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, 82152 Martinsried (Germany)

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Prof. Dr. Joëlle Vidal

Prof. Dr. Joëlle Vidal

Chimie et Photonique Moléculaires, Université de Rennes 1, CNRS UMR 6510, Bâtiment 10, Case 1012, Campus de Beaulieu, 35042 Rennes Cedex (France), Fax: (+33) 223-23-6955

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Prof. Dr. Michèle Reboud-Ravaux

Prof. Dr. Michèle Reboud-Ravaux

Enzymologie Moléculaire et Fonctionnelle, UR4-UPMC, Case 256, 6 eme Étage A, 7 Quai St-Bernard 75252 Paris Cedex 05 (France), Fax: (+33) 144-27-5022

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First published: 16 August 2010
Citations: 45

Graphical Abstract

Stop the shredder: The 20S proteasome maintains homeostasis and regulates important intracellular processes by subjecting most intracellular proteins to endoproteolytic cleavage. This complex hydrolysis machinery has received considerable attention for the treatment of many diseases, including cancer. We report a new set of noncovalent peptide mimics based on TMC-95A and our rational approach to inhibitor optimization using both crystallographic and kinetic studies.