Maeda M, Izuno Y, Kawasaki K, Kaneda Y, Mu Y, Tsutsumi Y, Nakagawa S, Mayumi T
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Chem Pharm Bull (Tokyo). 1998 Feb;46(2):347-50. doi: 10.1248/cpb.46.347.
Analogs of a partial sequence peptide of laminin, i.e., Tyr-Ile-Gly-Ser-Arg (YIGSR) analogs and Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg (CDPGYIGSR) analogs, were prepared by the solid-phase method and their inhibitory effects on experimental metastasis of B16-BL6 melanoma cells were examined. YIGSR analogs in which Ile was replaced by other hydrophobic amino acids (Met, Leu, Phe) were inhibitory. Cys-containing analogs of YIGSR were also prepared, but were less active than the parent peptide, YIGSR. Among them, CYIGSR was easily oxidized to form a disulfide bond. A Cys-containing YIGSR analog cyclized through a disulfide bond, cyclo(CYIGSRC)G, was prepared. The disulfide bond formation was performed on the resin by the silyl chloride-sulfoxide method and by the iodine oxidation method. The yield of the silyl chloride-sulfoxide method was much better than that of the iodine oxidation method.
层粘连蛋白部分序列肽的类似物，即酪氨酸 - 异亮氨酸 - 甘氨酸 - 丝氨酸 - 精氨酸（YIGSR）类似物和半胱氨酸 - 天冬氨酸 - 脯氨酸 - 甘氨酸 - 酪氨酸 - 异亮氨酸 - 甘氨酸 - 丝氨酸 - 精氨酸（CDPGYIGSR）类似物，通过固相法制备，并检测了它们对B16 - BL6黑色素瘤细胞实验性转移的抑制作用。异亮氨酸被其他疏水氨基酸（甲硫氨酸、亮氨酸、苯丙氨酸）取代的YIGSR类似物具有抑制作用。还制备了含半胱氨酸的YIGSR类似物，但活性低于母体肽YIGSR。其中，CYIGSR容易氧化形成二硫键。制备了一种通过二硫键环化的含半胱氨酸的YIGSR类似物，环（CYIGSRC）G。二硫键的形成通过树脂上的甲硅烷基氯 - 亚砜法和碘氧化法进行。甲硅烷基氯 - 亚砜法的产率比碘氧化法好得多。
