GD1α‐replica peptides functionally mimic GD1α, an adhesion molecule of metastatic tumor cells, and suppress the tumor metastasis

FEBS Letters

Ogino, Koichi³  Taki, Takao³  Hirabayashi, Yoshio¹  Ishikawa, Dai³  Kikkawa, Hironori²  Oku, Naoto² 

[1] Institute of Physical and Chemical Research, RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198, Japan;Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan;Cellular Technology Institute, Otsuka Pharmaceutical Co. Ltd., 463-10 Kagasuno, Kawauchi, Tokushima 771-0192, Japan

关键词: GD1α-replica peptide;    Phage-displayed random peptide library;    Adhesion molecule;    BSA;    bovine serum albumin;    ConA;    concanavalin A;    ELISA;    enzyme-linked immunosolvent assay;    HPTLC plate;    high-performance thin-layer chromatography plate;    HSE cell;    hepatic sinusoidal endothelial cell;    mAb;    monoclonal antibody;    PBS;    phosphate buffered saline;    SDS;    sodium dodecyl sulfate;    TBS;    trisaminomethane buffered saline;    TLC;    thin-layer chromatography;    GD1α;    NeuAcα2-3Galβ1-3(NeuAcα2-6)GalNAcβ1-4Galβ1-4Glcβ1-1Cer;   

DOI  :  10.1016/S0014-5793(98)01511-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A novel peptide technology to produce mimicking peptides of carbohydrate moiety (which we propose to name glyco-replica peptides) is a useful tool to elucidate the functions of glycoconjugate. Carbohydrate moiety of ganglioside GD1α functions as a molecule involved in the adhesion between murine highly metastatic lymphoma RAW117-H10 cells and hepatic sinusoidal endothelial (HSE) cells. To prepare peptides which mimic the carbohydrate structure of GD1α, phage clones expressing peptides which bound to a monoclonal antibody against GD1α (KA17) were isolated from a phage-displayed random peptide library. Four phage clones having affinity to the monoclonal antibody KA17 were isolated, and these clones showed inhibitory effect on the binding of KA17 to GD1α. The amino acid sequences of the displayed pentadecamers were determined, and one of the phages displaying sequence WHWRHRIPLQLAAGR bound to HSE cells directly and showed the highest inhibitory effect on the adhesion between RAW117-H10 cells and HSE cells. The synthesized peptides having the same sequences to the displayed 15mers in the four isolated phage clones also showed the inhibitory effect on the adhesion of RAW117-H10 cells to HSE cells, and, again, the WHWRHRIPLQLAAGR peptide showed the highest inhibitory effect. Furthermore, intravenous injection of the peptide brought almost complete inhibition of the metastasis of RAW117-H10 cells to lung and spleen, and about 50% inhibition of the liver metastasis. These results indicate that GD1α plays an important role for metastasis of RAW117-H10 cells, and the peptides obtained by the present procedure are able to mimic the functional role of the glycoconjugate.

【 授权许可】

Unknown