Novel Inhibitors of Tissue Transglutaminase

Tissue transglutaminase (TG2) is a protein that is able to mediate the cross-linking of other proteins. The unregulated activity of TG2 is implicated in fibrosis, celiac disease as well as cancer cell survival. Blocking this activity has been shown to decrease tumour size and growth in mice. We have previously designed small molecules that are highly effective at binding and blocking the activity of purified TG2, as has the Löser group. In this project, we will combine our design strategies to conceive more potent potent inhibitors, synthesize these inhibitors and test them against TG2, using activity assays developed in the Löser group. We will also take the best of these inhibitors and test them in cancer cells, to determine if they are both and selective. The results from this project will be used to design future molecules that are more selective for TG2, and will work more effectively inside human bodies as a cancer therapeutic.

Faculty Supervisor:

Jeff Keillor

Student:

Partner:

Helmholtz-Zentrum Dresden-Rossendorf

Discipline:

Life Sciences

Sector:

Health and Related Sciences & Technology; Pharmaceuticals; Life Sciences (not health)

University:

University of Ottawa

Program: