Toward the novel development for the diagnosis and treatment of cancer by the use of peptides that are accumulated into tumor cells.

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13680678
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Kinki University
• Principal Investigator: WAKAMIYA Tateaki Kinki University, School of science and engineering, professor, 理工学部, 教授 (10028243)
• Project Period (FY): 2001 – 2002
• Keywords: magnetic resonance imaging (MRI) / diagnosis and treatment of cancer / peptides accumulating into tumor cells / boron neutron capture therapy (BNCT) / pentafluorophenvlalanine / p-boronophenylalanine / 4-borono-2,3,5,6-tetrafluorophenylalanine

Research Abstract

1) Since commercial 4-fluorophenylalanine [Phe(4F)] is quite expensive, we synthesized this amino acid by conventional method from 4-fluorobenzyl chloride and diethyl acetamidomalonate. However, the content of F atom in this molecule is not enough for measurement by magnetic resonance imaging (MRI). Therefore, pentafluorophenylalanine [Phe(F_5)] was newly synthesized in a similar manner, and subjected to prepare several Phe(F_5)-containing dipeptides. Accumulation of these peptides into tunor cells via specific oligopeptide transporter is being currently undertaken.
2) p-Boronophenylalanine (Bpa) is rather expensive than Phe(4F), and the compound enriched with ^<10>B must be prepared by ourselves. To avoid the application of a harmful strategy such as the Snyder or Kirihata method, a novel methodology using p-bromobenzaldehyde as a starting material was elucidated. In the course of this study, we first planned to prepare N-chloroacetyl-Bpa (ClAc-Bpa) for enzymatic optical resolution. However, the synthesis of ClAc-Bpa was quite difficult, and we thus changed the plan toward to prepare common N-acetyl-Bpa (Ac-Bpa). As a result of the present study, we developed a useful method to prepare Ac-Bpa by employing the mild reaction conditions for boronation at para-position on the phenyl ring or halogenation at benzyl-position. Enzymatic optical resolution of this derivative is being currently undertaken.
3) During the course of this work, we newly planned to synthesize a chimeral compound between Bpa and Phe(F_5), i.e., 4-borono-2,3,5,6-tetrafluorophenylalanine [Bpa(F_4)], and we are currently undertaking the synthesis of this amino acid. Bpa(F_4)-ol that is obtainable by reduction of the carboxyl group of Bpa(F_4) seems to be a good candidate to promote boron neutron capture therapy (BNCT), i.e., we can check the exact location of cancer cells by MRI, and thus cancer cells can be irradiated accurately by neutron.