Synthesis of radiobromine-labeled antitumor peptides and application for theranostic probes

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591748
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Gunma University
• Principal Investigator: YAMADA Keiichi 群馬大学, 理工学府, 准教授 (70323334)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Aiko 群馬大学, 大学院医学系研究科, 寄付講座等教員 (80609032)
• Co-Investigator(Renkei-kenkyūsha): WATANABE Shigeki 独立行政法人日本原子力研究開発機構, 量子ビーム応用研究部門, 研究員 (10450305)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 抗腫瘍活性ペプチド / 放射性臭素 / 標識合成 / 治療的診断

Outline of Final Research Achievements

Triple negative breast cancer (TNBC) refers to any breast cancer that does not express the genes for hormone receptor and HER2/neu receptor. Unfortunately, TNBC cannot be treated with either hormone therapy and anti-HER2 antibody. Therefore, new targeted therapies are therefore an urgent unmet medical need for TNBC patients. We recently found that halogenated cyclic pentapeptides based on natural cyclic peptide sansalvamide A, namely SA-Br and SA-I, exhibit potent cytotoxicity to MDA-MB-231, one of the TNBC cell line. In this study, we tried to develop a theranostics probe based on radiobromine-labeled SA-Br and analogues. Initially, we developed a new method for preparing radiobromine-labeled peptides via silicon-halogen exchange reaction. Next, a series of cyclic peptides analogous to SA-I were synthesized via on-resin cyclization using oxime resin. Unfortunately, cytotoxicity of these peptides against MDA-MB-231 was much weaker than that of the parent peptide.

Free Research Field

合成化学