Synthetic Study of Peptides Accumulating into Tumor Cells for the Diagnosis and Treatment of Cancer.

积累到肿瘤细胞中的肽的合成研究用于癌症的诊断和治疗。

• 批准号: 11680593
• 负责人: WAKAMIYA Tateaki
• 金额: $ 2.37万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680593/
• 关键词: 4-Fluorophenylalanine; Oligopeptide Transporter; Cancer; p-Boronophenylalanine; Peptides Accumulating into Tumor Cells; Positron Emission Tomography; Boron Neutron Capture Theraph; Nuclear Magnetic Resonance Imaging Method; ホウ素-10; 4-フルオロテラニン含有ペプ

In the first year of this project, nine kinds of 4-fluorophenylalanine [Phe(4F)] containing peptides were synthesized. These peptides were accumulated into some kinds of tumor cells via specific oligopeptide transporter. This result suggests that Phe(4F)-containing peptides can be utilized for the diagnosis of cancer based on the positron emission tomography (PET). For this purpose, however, we have to newly develop a convenient method for the preparation of Phe(4F) labeled with ^<18>F.In the second year, three kinds of p-boronophenylalanine (Bpa) containing peptides with serine, glutamic acid and lysine as C-terminal amino acid, respectively. These peptides are 300-fold more soluble in water than Bpa, and their accumulation into tumor cells are comparable to that of Bpa. The results suggest that Bpa-containing peptides may be good candidates for boron neutron capture therapy (BNCT) of cancer. From a viewpoint of necessity of Bpa as very valuable ^<10>B carrier, we developed a novel and secure method to prepare Bpa.p-Boronophenylalaninol (Bpa-ol) reported by Kirihata et al.is also useful compound as a ^<10>B carrier. In the present study, we synthesized a hybrid compound between Bpa and Bpa-ol, and are currently undertaking the measurement of their accumulation into tumor cells as well as their tumor cell killing effect.As a result of present study, we newly planned to elucidate nuclear magnetic resonance imaging method for the diagnosis of cancer using Phe(4F)- or Bpa-containing peptides that accumulate specifically into tumor cells.

在本项目的第一年，合成了9种含4-氟苯丙氨酸[Phe（4F）]的肽。这些肽通过特异性的寡肽转运蛋白在某些肿瘤细胞中积累。该结果表明，含有Phe（4F）的肽可用于基于正电子发射断层扫描（PET）的癌症诊断。第二年，我们成功地合成了三<18>种分别以丝氨酸、谷氨酸和赖氨酸为C-末端氨基酸的对硼苯丙氨酸（Bpa）肽。这些肽在水中的溶解度是Bpa的300倍，它们在肿瘤细胞中的积累与Bpa相当。结果表明，含BPA的肽可能是硼中子俘获治疗（BNCT）的癌症的良好候选者。从Bpa作为非常有价值的^ B载体的必要性的观点<10>出发，我们开发了一种新的和安全的方法来制备Bpa。Kirihata等人报道的对硼苯基丙氨酸醇（Bpa-ol）al.is也是作为^ B载体的有用化合物<10>。本研究合成了Bpa和Bpa-ol的杂合化合物，测定了它们在肿瘤细胞中的蓄积和对肿瘤细胞的杀伤效果。根据本研究的结果，新计划阐明利用特异性蓄积在肿瘤细胞中的Phe（4F）或Bpa的肽进行癌症诊断的核磁共振成像方法。

项目成果

若宮建昭 他5名: "Synthesis of p-Boronophenylalanine-Containing Peptides for Boron Neutron Capture Therapy of Cancer Cells."Peptide Science 1999. 209-212 (2000)

Takeaki Wakamiya 等 5 人：“用于癌细胞硼中子捕获疗法的含对硼苯丙氨酸肽的合成”，肽科学 1999 年。209-212 (2000)

T.Wakamiya, T.Yamashita, T.Fujii, Y.Yamaguchi, T.Nakano, and M.Kirihata: "Synthesis of p-Boronophenylalanien-Containing Peptides for Boron Neutron Capture Therapy of Cancer Cells."Peptide Science. 1999. 209-212 (2000)

T.Wakamiya、T.Yamashita、T.Fujii、Y.Yamaguchi、T.Nakano 和 M.Kirihata：“用于癌细胞硼中子捕获疗法的含对硼苯丙氨酸肽的合成”。肽科学。

若宮建昭 他5名: "Synthesis of p-Boronophenylalanine-Containing Peptidas for Boron Neutron Capture Therapy of Cancer Cells"Peptide Science 1999. 209-212 (2000)

Takeaki Wakamiya 等 5 人：“Synthesis of p-Boronophenalanine-Containing Peptidas for Boron Neutron Capture Therapy Therapy of Cancer Cells” Peptide Science 1999. 209-212 (2000)

若宮建昭: "Synthesis of p-Boronophenylalanine-Containing Peptides for Boron Neutron Capture Therapy of Cancer Cells."Peptide Science 1999. (印刷中). (2000)

Takeaki Wakamiya：“用于癌细胞硼中子捕获疗法的含对硼苯丙氨酸肽的合成”。肽科学 1999 年（出版中）。