The isolation and characterisation of Transglutaminase 2 inhibitors from natural sources

Transglutaminases are calcium dependent enzymes which are involved in a variety of human disease conditions. Nine different isotypes of transglutaminases have been described including transglutaminase 2 (TG2) which is the most well characterised isotype. Transglutaminases possess a range of different catalytic activities including; the posttranslational modification of proteins by the formation of ɛ-(ƴ-glutamyl) lysine cross links between two or more proteins, the incorporation of polyamine into proteins and the deamidation of protein bound glutamine to glutamate. In coeliac disease the deamidating activity of TG2 in the intestinal lamina propria converts glutamine to glutamate in undigested gliadin peptides. This conversion elicits an immune response which causes the typical symptoms of coeliac disease. Currently the only treatment for coeliac disease is a gluten free diet. The TG2 inhibitors are the potential therapeutic agents against the coeliac disease however the current chemically synthesised TG2 inhibitors have toxicity problems. Moreover, the progress in the treatment of coeliac disease is hampered by no suitable animal model for coeliac disease and the lack of a suitable TG2 deamidation assay with which to test potential inhibitors.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

Nottingham Trent University

Year dc:date.issued

2014

Author dc:creator

• Aldubayan, M