Targeting gamma-glutamyl transpeptidase: A pleiotropic enzyme involved in glutathione metabolism and in the control of redox homeostasis.

Gamma-glutamyl transpeptidase (GGT) is an enzyme located on the outer membrane of the cells where it regulates the metabolism of glutathione (GSH), the most abundant intracellular antioxidant thiol. GGT plays a key role in the control of redox homeostasis, by hydrolyzing extracellular GSH and providing the cell with the recovery of cysteine, which is necessary for de novo intracellular GSH and protein biosynthesis. Therefore, the upregulation of GGT confers to the cell greater resistance to oxidative stress and the advantage of growing fast.

Amphiphilic Cationic Triscyclometalated Iridium(III) Complex-Peptide Hybrids Induce Paraptosis-like Cell Death of Cancer Cells via an Intracellular Ca-Dependent Pathway.

We report on the design and synthesis of a green-emitting iridium complex-peptide hybrid (IPH) , which has an electron-donating hydroxyacetic acid (glycolic acid) moiety between the Ir core and the peptide part. It was found that is selectively cytotoxic against cancer cells, and the dead cells showed a green emission. Mechanistic studies of cell death indicate that induces a paraptosis-like cell death through the increase in mitochondrial Ca concentrations via direct Ca transfer from ER to mitochondria, the loss of mitochondrial membrane potential (ΔΨ), and the vacuolization of cytoplasm and intracellular organelle.