Structure-activity relationships of hydrophobic alkyl acrylamides as tissue transglutaminase inhibitors.

ABSTRACT: Tissue transglutaminase (TG2) is a multifunctional protein that plays biological roles based on its ability to catalyse protein cross-linking and to function as a non-canonical G-protein known as Ghα. The non-regulated activity of TG2 has been implicated in fibrosis, celiac disease and the survival of cancer stem cells, underpinning the therapeutic potential of cell permeable small molecule inhibitors of TG2. In the current study, we designed a small library of inhibitors to explore the importance of a terminal hydrophobic moiety, as well as the length of the tether to the irreversible acrylamide warhead. Subsequent kinetic evaluation using an in vitro activity assay provided values for the k _inact and K _I parameters for each of these irreversible

SUBMITTER: Rangaswamy AMM 

PROVIDER: S-EPMC9020614 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature