Luzi Jakob Barandun

 

PhD Student

Location:

HCI G-327

Phone:

+41-44-633 47 42

e-mail:

Luzi Jakob Barandun

Education

2004-2008:

BSc and MSc Study in Chemistry at ETH Zürich

2008:

Master thesis with Prof. F. Diederich, ETH Zurich

2008-2009:

Internship at Novartis, Basel

since 2009:

PhD with Prof. F. Diederich at ETH Zurich

 

Protein-Protein Interactions as a Drug Target: Structure-Based Design and Synthesis of tRNA-Guanine Transglycosylase (TGT) Inhibitors

Protein-protein interactions play a key role in most biological processes. The controlled modulation of a protein complex would offer great opportunities for therapeutic intervention. However, the development of such inhibitors is an enormous challenge.
The goal of this project is the structure-based design and synthesis of drug-like inhibitors that can modulate the dimerization of Z. mobilis tRNA-guanine transglycosylase (TGT). A structural closely related TGT is found in Shigella bacteria, which cause bacterial dysentery or shigellosis - a disease affecting more than 160 million people and claiming 1.1 million deaths per year. The recent occurrence of multi drug-resistant strains necessitates the development of novel innovative drugs. It has been shown that the virulence of Shigella is closely linked to TGT. Although, TGT enzymes are present in bacteria and humans, different substrate specificity makes the selective inhibition of the bacterial enzyme possible. Hence, TGT represents an attractive target for the treatment of shigellosis.

Crystal structure (PDB code: 1Q2S) of Z. mobilis TGT bound to a RNA substrate.
W. Xie, X. Liu, R. Huang, Nature Struct. Biol. 2003, 10, 781-788.

Publications

A. K. H. Hirsch, M. S. Alphey, S. Lauw, M. Seet, L. Barandun, W. Eisenreich, F. Rohdich, W. N. Hunter, A. Bacher, F. Diederich, Org. Biomol. Chem. 2008, 6, 2719-2730. Inhibitors of the Kinase IspE: Structure-Activity Relationships and Co-Crystal Structure Analysis.

M. Zürcher, F. Hof, L. Barandun, A. Schütz, W. B. Schweizer, S. Meyer, D. Bur, F. Diederich, Eur. J. Org. Chem. 2009, 11, 1707-1719. Synthesis of exo-3-Amino-7-azabicyclo[2.2.1]heptanes as a Class of Malarial Aspartic Protease Inhibitors: Exploration of Two Binding Pockets.

L. J. Barandun, F. Immekus, P. C. Kohler, S. Tonazzi, B. Wagner, S. Wendelspiess, T. Ritschel, A. Heine, M. Kansy, G. Klebe, F. Diederich, Chem. Eur. J. 2012, 18, 9246-9257. From lin-Benzoguanines to lin-Benzohypoxanthines as Ligands for Z. mobilis TGT: Replacement of Protein-Ligand Hydrogen Bonding by Import of Water Clusters.

S. Riniker, L. J. Barandun, F. Diederich, O. Krämer, A. Steffen, W. F. van Gunsteren, J. Comput Aided Mol. Des. 2013, DOI 10.1007/s10822-012-9620-8. Free enthalpies of replacing water molecules in protein binding pockets.

Last update: December 2012