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. γ‐Glutamyl cyclotransferase (GGCT) converts γ‐glutamyl amino acids into pyroglutamic acid and the corresponding amino acids. The singular substrate preference had long hampered its chemical probe development. In this context, we designed fluorogenic GGCT probe (LISA‐101) and fluorescent‐tagged inhibitor (gKFA). Here, we report how we designed these chemical biology‐oriented compounds.
Source: Journal of Peptide Science - Category: Biochemistry Authors: Tags: Special Issue Article Source Type: research