Dept. of Biochemistry & Organic Chemistry

Thomas Gossas, MSc

PhD Thesis

Protease Activity, Inhibition and Ligand Interaction Analysis: Developments and Applications for Drug Discovery

Research

The main interest of my research is enzyme-ligand interactions, and the enzymes I study are proteases. Proteases are recognized as important drug targets. Hepatitis C, COPD, MS and cancer are some of the diseases that could potentially be cured by protease inhibitors. Therefore the development of methods to study inhibition and protease-inhibitor interactions is an important part of the research. The methodologies in use are activity-based assays and interaction assays using SPR-biosensor technology. These methods are used for the characterization of protease interactions with both naturally occurring ligands, to elucidate their normal physiological function and regulation, and synthetic compounds, with the ultimate aim to discover novel drugs. Thus, the research contributes to the development of inhibitors against the specific enzymes under study as well as increasing the general knowledge about protein-ligand interactions and learning how such knowledge can be implemented in drug discovery projects. This will accelerate the development of drugs for a number of major diseases.

Enzymology and drug discovery

 

Publications

1. Örtqvist, P., Peterson, S.D., Åkerblom, E., Gossas, T., Sabnis, Y.A., Fransson, R., Lindeberg, G., Danielson, U.H., Karlén, A. and Sandström, A. (2007) Phenylglycine as a Novel P2 Scaffold in Hepatitis C Virus NS3 Protease Inhibitors. Bioorganic & Medicinal Chemistry 15:1448-1474.
2. Gossas, T. and Danielson, U.H. (2006) Characterization of Ca2+ Interactions with Matrix Metallopeptidase-12: Implications for Matrix Metallopeptidase regulation. Biochemical Journal 398: 393-398.
3. Robert Rönn, Yogesh A. Sabnis, Thomas Gossas, Eva Åkerblom, U. Helena Danielson, Anders Hallberg and Anja Johansson. (2006) Exploration of acyl sulfonamides as carboxylic acid replacements in protease inhibitors of the hepatitis C virus full-length NS3. Bioorganic & Medicinal Chemistry 14(2):544-59.
4. Gossas T, Danielson UH. Analysis of the pH-dependencies of the association and dissociation kinetics of HIV-1 protease inhibitors.
   J Mol Recognit. 2003 Jul-Aug;16(4):203-12.