These potent molecules are side chain modified peptides. The electrophilic “DON” group replaces the substrate glutamine. The active site cysteinyl residue attacks the carbonyl group (1). The subsequent reaction leads to the release of nitrogen (2) and the concomitant irreversible alkylation at the active site of the transglutaminases (3).
Zedira developed molecules frequently used in scientific literature.
Z-DON (Z006; Z-DON-Val-Pro-Leu-OMe) Z-DON is a very potent and specific blocker of tissue transglutaminase (IC50 about 0.02 μM) and membrane permeable.
Boc-DON (B003; Boc-DON-Gln-Ile-Val-OMe) Boc-DON is a potent and specific blocker of tissue transglutaminase (IC50 about 0.3 μM) and is not membrane permeable.
K9-DON (K003; Ac-LGPG-DON-SLVIG-NH2) K9-DON was developed to block coagulation factor XIIIa. The sequence is derived from a casein peptide. The IC50 is about 0.8 μM (Sabo et al. Biochemistry 2007, 46:10089-101).
TAMRA-DON (R002; N-(Tetramethylrhodaminyl)-DON-Val-Pro-Leu-OMe) TAMRA-DON is a fluorescent blocker of tissue transglutaminase with an IC50 of about 0.1 μM.