Marie Curie Research Training Network
TRACKS
Transglutaminases: role in pathogenesis, diagnosis and therapy (TRACKS)
| Objectives | Researchers | People Involved | News Update | Vacancies |
Objective 5 : TGase Inhinitors
Based on results obtained with previously developed inhibitors found in the literature, published patents,analysis of chemical databases and the use of protein modelling, since the crystallographic structure of three of the eight human TGs is known, the objective is to develop highly specific site-directed inhibitors for these enzymes with initial emphasis on TG2.
Rapid assay methods developed in Objective 6 will aid in inhibitor screening.this is particulary pertinent for the screening of compounds from chemical databases.Two types of inhibitors will be studied, one permeable and one impermeable to the cell membrane in order to be able to target the primary TG involved at the site of its action(eg both TG2 and Factor XIII work predominantly in the extracellular environment under normal physiological conditions) and aid in specificity.
Aston University, UK and Tampere University, Finland have already filed patents or published on TG-targeted but TG-generic inhibitors (patent application WO 2004/113363 A2 Griffin,Coutts,Saint.: Markku and colleagues Chem. Biol 2003;10 (3): 225-231) which will act as a valuable starting point. Inhibiting antibodies and their fragments developed in Objective 4 will also be screened and used where applicable. We will investigate (Objectives 1,2 and 3) how these inhibitors interfere with the modulation of the TG mediated diseases targeted in this proposal using both cell and experimental models.
