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佐々木 一郎; 渡辺 茂樹; 大島 康宏; 須郷 由美; 山田 圭一*; 花岡 宏史*; 石岡 典子
Peptide Science 2015, p.243 - 246, 2016/03
Radioisotope labeled peptides with high affinity to receptors overexpressing on the surface of tumor cells are promising for applications in nuclear medicine such as diagnostic radiography and radiotherapy. Radiohalogens such as I and
At are useful for clinical imaging and therapeutic applications, and it can be introduced at the
position of phenylalanine residue via electrophilic destannylation. KCCYSL (Lys
-Cys
-Cys
-Tyr
-Ser
-Leu
) is a hexapeptide containing disulfide bond. Previous study revealed that KCCYSL has potential as tumor imaging and therapeutic agent targeting tumor cells overexpressing the human epidermal growth factor receptor type 2 (HER2). In this study, we report synthesis and
evaluation of radiohalogenated KCCYSL derivatives. Precursor peptides, Boc-F(
-SnBu
)K(Boc)C(Trt)C(Trt)Y(
Bu)S(
Bu)L-OH and Boc-F(
-SnBu
)GS(
Bu)GK(Boc)C(Trt)C(Trt)Y(
Bu)S(
Bu)L-OH, were synthesized by the Fmoc solid phase peptide synthesis. Then, precursor peptides were radioiodinated via electrophilic destannylation, and they were deprotected to obtain F(
-
I)KCCYSL and F(
-
I)GSGKCCYSL in radiochemical yield 15% and 17%, respectively.
assays of the radioiodinated peptides for HER2 and stability in serum are being undertaken.
佐々木 一郎; 花岡 宏史*; 山田 圭一*; 渡辺 茂樹; 須郷 由美; 大島 康宏; 鈴木 博元; 石岡 典子
Peptide Science 2014, p.257 - 260, 2015/03
We have sought to establish drug discovery system using radioisotope (RI) labeled peptides which have high affinity to target proteins overexpressed in cancers. Of the target proteins, we chose the human epidermal growth factor receptor type 2 (HER2), a membrane protein overexpressed in various cancers to evaluate the drug discovery system. Three series of random hexapeptide libraries introduced a radioiodinated D-tyrosine (y(3-I)) to
-terminal were designed and binding assay with HER2-expressed cell lines were conducted in this study. First, we synthesized a series of random hexapeptide libraries with fixed amino acid sequence at 1 and 2 positions, y(3-
I)X
X
X
X
X
X
. Non-radioactive random peptide libraries, yXXXXXX, were prepared by Fmoc-SPPS with an automatic peptide synthesizer. Radioiodinated y(3-
I)XXXXXX were subsequently synthesized in 30-50% radiochemical yield. Binding assay using HER2-overexpressed cell line showed that high affinity (38-50% dose, n=6) was obtained with yIIXXXX, while other random peptide libraries were yielded low affinity (approximately 1% dose), which indicated that the system using RI labeled random peptide libraries have potential to discover peptide drug for cancer therapy. Preparation of other random hexapeptide libraries are being undertaken.