Christoph Fäh


PhD Student


HCI G-328


+41-44-633 4741


Christoph Fäh



Study of Chemistry at ETH Zurich


Exchange semester at Strathclyde University Glasgow


Diploma thesis with Prof. F. Diederich at ETH Zuerich


Internship at Hoffmann-La Roche AG, Basel

since 2005:

PhD with Prof. F. Diederich at ETH Zuerich

De novo Design of Nonpeptidic Inhibitors of the Malarial Protease Plasmepsin II

Pepstatin A bound to Plasmepsin II.

Malaria is the most widespread parasitic disease in man, with about 2 billion people at risk of infection, mainly in the tropical and subtropical areas of the world. The appearance of drug resistant parasites has reduced the effectiveness of most antimalarial drugs and new possible targets are of great interest. The proteolytic enzyme Plasmepsin II has been proposed as a new therapeutic target. Plasmepsin II is a malarial aspartic protease which is envolved in the hemoglobin degradation. Plasmepsin I and IV, two aspartic proteases as well, and Histo-Aspartic-Protease (HAP) are also acitve in the hemoglobin degradation pathway. Their high sequence homology towards Plasmepsin II gives the possibility to design adaptive Inhibitors to inhibit all four enzymes. This would lead to a faster starvation of the parasite and retard the appearance of drug resistant mutants, since the parasite will have to mutate several proteins to overcome inhibiton. It is the aim of the project to find new nonpeptidic inhibitors for Plasmepsin II, which also are active for Plasmepsin I, IV and HAP. Inhibitor design will be done on the basis of crystal structures with MOLOC, a modeling program developed by Hoffmann-La Roche AG in Basel.


C. Faeh, H. Kuehne, T. Luebbers, P. Mattei, C. Maugeais, P. Pflieger, U.S. Pat. Appl. Publ. 2007, 23pp. Preparation of heteroaryl and benzyl amide compounds as CETP inhibitors for treating dyslipidemia and other diseases.

K. Mueller, C. Faeh, F. Diederich, Science 2007, 317, 1881-1886. Fluorine in Pharmaceuticals: Looking Beyond Intuition.

E. Schweizer, A. Hoffmann-Röder, K. Schärer, J. A. Olsen, C. Fäh, P. Seiler, U. Obst-Sander, B. Wagner, M. Kansy, F. Diederich, ChemMedChem 2006, 1, 611-621. A Fluorine Scan at the Catalytic Center of Thrombin: C-F, C-OH, and C-OMe Bioisosterism and Fluorine Effects on pKa and log D Values.

F. Hof, A. Schütz, C. Fäh, S. Meyer, D. Bur, J. Liu,D. E. Goldberg, F. Diederich, Angew. Chem. Int. Ed. 2006, 45, 2138-2141. Starving the malaria parasite: Inhibitors active against the aspartic proteases plasmepsins I, II, and IV.

last update: October 2006