GD1α-replica peptides functionally mimic GD1α, an adhesion molecule of metastatic tumor cells, and suppress the tumor metastasis
GD1α-replica peptides functionally mimic GD1α, an adhesion molecule of metastatic tumor cells, and suppress the tumor metastasis
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DOI：
10.1016/s0014-5793(98)01511-7
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发表时间：
1998-12-11
期刊：
影响因子：
3.5
通讯作者：
Taki, T
中科院分区：
文献类型：
--
作者：
Ishikawa, D;Kikkawa, H;Taki, T
一种新的制备碳水化合物部分的模拟多肽(我们建议将其命名为糖复制多肽)的多肽技术是阐明糖共轭功能的有用工具。神经节苷脂Gd1α的糖基部分参与了小鼠高转移性淋巴瘤RAW117-H10细胞与肝窦内皮细胞之间的黏附。为了制备模拟Gd1α糖结构的多肽，仅从噬菌体展示的随机多肽库中分离表达与抗Gd1α单抗(XA17)结合的多肽的噬菌体克隆。仅分离到4个与单抗KA17有亲和力的噬菌体克隆，这些克隆对KA17与Gd1α的结合具有抑制作用。对展示的十五聚体的氨基酸序列进行了测定，其中一个展示序列WHWRHRIPLQLAAGR与HSE细胞直接结合，对RAW117-H10细胞与HSE细胞的黏附抑制作用最强。4个噬菌体克隆中与所展示的15聚体序列相同的合成肽对RAW117-H10细胞与HSE细胞的黏附也有抑制作用，其中WHWRHRIPLQLAAGR肽的抑制作用最强。静脉注射可几乎完全抑制RAW117-H10细胞对肺、脾的转移，对肝转移的抑制率约为50%。这些结果表明Gd1α在RAW117-H10细胞的转移中起重要作用，并且通过本方法获得的多肽能够模拟糖共轭的功能作用，(C)1998欧洲生化学会联合会。
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 GD1 alpha 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 GD1 alpha, phage clones expressing peptides which bound to a monoclonal antibody against GD1 alpha (XA17) mere isolated from a phage-displayed random peptide library. Four phage clones having affinity to the monoclonal antibody KA17 mere isolated, and these clones showed inhibitory effect on the binding of KA17 to GD1 alpha. 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 GD1 alpha 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, (C) 1998 Federation of European Biochemical Societies.