Design of fluorogenic probes and fluorescent-tagged inhibitors for γ-glutamyl cyclotransferase

A tumor-related protein, human chromosome 7 ORF 24 (C7orf24), is involved in regulation of the glutathione homeostasis cycle as a γ-glutamyl cyclotransferase (GGCT). The singular substrate preference of this enzyme had long hampered its chemical probe development. That is, substrate of GGCT is definitely ‘γ-Glu-Xaa’, where Xaa is an L-α-amino acid. Based on the structure of substrates and GGCT fluorogenic probes, LISA-4/101, we succesfully developed a fluorescent-tagged inhibitor, gKFA. These chemical tools will assist cancer-related researches in the future. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.