Synthesis of gamma-glutamyl transpeptidase-specific chemical probes and their application to cancer immunotherapy

• Project/Area Number: 15K21117
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bioorganic chemistry; Biomolecular chemistry
• Research Institution: Kyoto University
• Principal Investigator: WATANABE Bunta 京都大学, 化学研究所, 助教 (10544637)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: γ-グルタミルトランスペプチダーゼ / GGT / 酵素阻害剤 / GGsTop / 分子プローブ / 抗体依存性細胞傷害

Outline of Final Research Achievements

Four novel chemical probes based on the structure of GGsTop, a potent and selective γ-glutamyl transpeptidase (GGT) inhibitor, were designed and synthesized. One of theses probes inhibited human GGT strongly. These results opened the gate to the development of novel ligands that could exert antibody-dependent cellular cytotoxicity against various cancer cells overexpressing GGT on their cell surfaces.