ANTI-TUMOR EFFECTS OF NOVEL IMMUNOACTIVE PEPTIDES, FK-156 AND ITS SYNTHETIC DERIVATIVES
ANTI-TUMOR EFFECTS OF NOVEL IMMUNOACTIVE PEPTIDES, FK-156 AND ITS SYNTHETIC DERIVATIVES
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DOI：
10.7164/antibiotics.36.566
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发表时间：
1983-01-01
影响因子：
3.3
通讯作者：
IMANAKA, H
中科院分区：
文献类型：
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作者：
IZUMI, S;NAKAHARA, K;IMANAKA, H
通过肿瘤内或全身应用FK-156（N-[Na-（γ- D-谷氨酰）-L-赖氨酰]-D-丙氨酸）及其合成衍生物对同系[白血病] P388-DBA/2小鼠系统的作用。在测试的21种化合物中，FK-156、FK-565（谷蛋白）、FR-46758（庚酰基-D-谷氨酰基-[D-（4-氨基-5-羟基戊基）-L-甘氨酰基]-D-丙氨酸）、FR-48217（十二烷基-L-丙氨酰基-D-谷氨酰基-L-α，. . -二氨基庚二酰-D-丙氨酸），（FR-46091（硬脂酰-D-谷氨酰-L-α，. . -二氨基庚二酰-L-甘氨酸）和FR-47920（硬脂酰-D-谷氨酰-L-α，. -当直接注射到肿瘤块中时，FK-156、FK-565和FR-46758（二氨基庚二酸）基本上抑制肿瘤生长，并且进一步的实验显示，即使当皮下施用时，FK-156、FK-565和FR-46758也是有效的。进入远离肿瘤的部位。由于这3种化合物在体外对P388细胞的细胞毒性很低，因此强烈建议其生长抑制机制是宿主介导的。FK-565单次给药可显著降低健康DBA/2小鼠的体重，而FK-156和FR-46758则无此作用。这些结果表明，FK-156和FR-46758作为免疫抑制剂在治疗癌症的安全性方面优于FK-565。尽管在任一系统中6种化合物的2次注射方案中均未观察到显著的寿命延长，但全身多次注射FK-156和FR-46758使P388荷瘤小鼠的中位生存时间在统计学上显著延长。
Effects produced by intratumor or systemic application of FK-156 (N-[Na-(.gamma.-D-glutamyl)-L-lysyl]-D-alanine) and its synthetic derivatives on the syngeneic [leukemia] P388-DBA/2 mouse system were investigated. Among 21 compounds tested, FK-156, FK-565 (gludapcin), FR-46758 (heptanoyl-D-glutamyl-[D-(4-amino-5-hydroxypentyl)-L-glycyl]-D-alanine), FR-48217 (lauryl-L-alanyl-D-glutamyl-L-.alpha.,.epsilon.-diaminopimelyl-D-alanine), (FR-46091 (stearyl-D-glutamyl-L-.alpha.,.epsilon.-diaminopimelyl-L-glycine) and FR-47920 (stearyl-D-glutamyl-L-.alpha.,.epsilon.-diaminopimelic acid) substantially suppressed tumor growth when directly injected into a tumor mass and further experiments showed that FK-156, FK-565 and FR-46758 were effective even when administered s.c. into site remote from tumor. The mechanisms of growth inhibition are strongly suggested to be host mediated, because these 3 compounds have remarkably low cytotoxicity against P388 cells in vitro. A single dose of FK-565 markedly decreased body weight in healthy DBA/2 mice, whereas FK-156 and FR-46758 did not. These results indicate the superiority of FK-156 and FR-46758 as immunotherapeutic agents over FK-565 with respect to their safety for treatment of cancer. Although significant life-span prolongation could not be seen in the 2-injection regimen of 6 compounds in either system, systemic multiple injections of FK-156 and FR-46758 provided a statistically significant increase in the median survival time of P388 tumor-bearing mice.