Manuel Ellermann


PhD Student


HCI G-320


+41-44-632 2955


Manuel Ellermann



Study of Chemistry at University of Stuttgart and Philipps-University, Marburg


Internship at Imperial College London, UK, with J. Steinke


Diploma Thesis with T. Schrader, Philipps-University, Marburg

since 2005:

Graduate Student with F. Diederich, ETH Zurich

Design, Synthesis and Evaluation of novel Bisubstrate-Inhibitors of Catechol-O-Methyltransferase (COMT)

The enzyme catechol-O-methyltransferase (COMT) catalyzes the methyl group transfer from the cofactor S-adenosylmethionine (SAM) to the hydroxy group of catechol-type substrates, such as L-DOPA and dopamine. The inhibition of COMT is of significant interest in the L-DOPA-based treatment of Parkinson's disease, since it ensures that a higher quantity of orally administered L-DOPA reaches its target in the brain.
A bisubstrate-inhibition approach led to compound 1 with an IC50 of 9 nanomolar. The binding conformation of 1 in the active site of COMT was revealed by X-ray crystallography (in collaboration with Roche, Basel). Recently, we have been able to substitute for the first time the nitro group in 1 by suitable hydrophobic residues without substantial loss in activity. Replacement of the nitro group is desirable for both pharmacokinetic and pharmacological reasons. In ongoing work, we are using computational modeling (MOLOC) and advanced synthesis in order to investigate suitable improvements for inhibitor 1.

Crystal structure of the ternary complex between COMT, Mg++ and the bisubstrate inhibitor 1.


M. Maue, K. Bernitzki, M. Ellermann, T. Schrader, Synthesis-Stuttgart 2008, 2247-2256. Bifunctional Bisamphiphilic Transmembrane Building Blocks for Artificial Signal Transduction.

T. Schrader, M. Maue, M. Ellermann, Journal Of Receptors And Signal Transduction 2006, 26, 473-485. Entirely Artificial Signal Transduction with Adrenaline.

M. Ellermann, R. Jakob-Roetne, C. Lerner, E. Borroni, D. Schlatter, D. Roth, A. Ehler, M. G. Rudolph, F. Diederich, Angew. Chem. Int. Ed. 2009, 48, 9092–9096. Angew. Chem., 2009, 121, 9256–9260. Molecular Recognition at the Active Site of Catechol-O-Methyltransferase: Energetically Favorable Replacement of a Water Molecule Imported by a Bisubstrate Inhibitor.

last update: Mar. 2009