Tobias Kissling


PhD Student


HCI G-314


+41-1-632 2636


Tobias Kissling



Study of chemistry, University of Bern


Research stage with Prof. A. P. Rauter, FCUL Lisbon


Diploma thesis with Prof. P. Renaud, University of Bern

since 2004:

PhD with Prof. F. Diederich, ETH Zürich

From Fragments to Leads for New Alzheimer Medicines – Structure-based Design and Synthesis of Novel Beta-Secretase-Inhibitors

About 5 % of people older than 60 years are suffering from dementia. In western countries Alzheimer’s disease is responsible for about 2/3 of the cases. In Switzerland, Alzheimer’s disease is the most frequent cause of death after cardiovascular diseases, cancer and stroke. Alzheimer’s disease is of growing importance in our society because of the increasing life expectancy thanks to modern medicine. Currently there is no cure for Alzheimer’s disease and the available treatments are rather unsatisfactory. Therefore there is an urgent need for new Alzheimer Medicines.

β-secretase (BACE) is a key enzyme involved in the formation of the toxic protein amyloid-β. Aggregation of amyloid-β leads to amyloid plaques – pathological protein depositions found in the brains of patients suffering from Alzheimer’s disease. BACE has been identified as a promising drug target by studies with BACE knockout mice showing that these mice are viable and fertile.

Active-site of β-Secretase shown with Inhibitor (PDB code: 1W51)

The results of a fragment-screening and the crystal structures published in the PDB (Protein Data Base) serve as the basis for the rational design of novel lead structures using the modeling-software MOLOC. The defined target molecule and some interesting analogues will be synthesized and their biological activity will be tested.