Characterization of a Novel Human Tumor Necrosis Factor‐α Mutant with Increased Cytotoxic Activity
Characterization of a Novel Human Tumor Necrosis Factor‐α Mutant with Increased Cytotoxic Activity
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细胞毒活性增强的新型人肿瘤坏死因子-α 突变体的表征
DOI：
10.1111/j.1349-7006.1995.tb02990.x
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Y. Niitsu
中科院分区：
文献类型：
--
作者：
T. Masegi;A. Kato;K. Kitai;M. Fukuoka;H. Ogawa;Y. Ichikawa;Satoshi Nakamura;N. Watanabe;Y. Niitsu
利用蛋白质工程技术制备了各种新型重组人肿瘤坏死因子-α（TNF）突变体，并将其细胞毒活性与完整形式的TNF（完整TNF）进行了比较。突变体 471（一种在氨基末端删除 7 个氨基酸并用 ArgLysArg 取代 Pro8Ser9Asp10 的 TNF 突变分子）对小鼠 L929 细胞的细胞毒活性高出 6 倍。突变体 TNF 与小鼠 L929 成纤维细胞上的 TNF 受体结合的能力增强。一项交联研究表明，突变体 471 形成活性三聚体的能力增强。突变体 471 对人 KYM 肌瘤细胞和人 MIA PaCa-2 胰腺癌细胞也表现出更高的细胞毒活性。突变体可能的恶病素活性几乎与完整的 TNF 相同。这些结果表明突变体 471 可能是比完整 TNF 更有前景的抗癌药物候选者。
Various novel recombinant human tumor necrosis factor‐α (TNF) mutants were prepared using protein engineering techniques, and their cytotoxic activity was compared with that of the intact form of TNF (intact TNF). Mutant 471 (a TNF mutant molecule with the deletion of 7 amino acids at the amino‐terminal and the substitution of Pro8Ser9Asp10 by ArgLysArg) had a 6‐fold higher cytotoxic activity against murine L929 cells. The mutant TNF had an increased ability to bind to TNF receptor on murine L929 fibroblasts cells. A cross‐linking study revealed that mutant 471 had an increased ability to form an active trimer. Mutant 471 also showed higher cytotoxic activity against human KYM myosarcoma cells and human MIA PaCa‐2 pancreatic carcinoma cells. The possible cachectin activity of the mutant was almost the same as that of intact TNF. These results suggest that mutant 471 might be a more promising candidate as an anticancer agent than intact TNF.
DOI：
10.1016/s0021-9258(18)48183-5
发表时间：
1987-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Smith;C. Baglioni
通讯作者：
R. Smith;C. Baglioni
肿瘤坏死因子增加人成纤维细胞上表皮生长因子受体的数量。
DOI：
--
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Palombella,VJ;Yamashiro,DJ;Maxfield,FR;Decker,SJ;Vilcek,J
通讯作者：
Vilcek,J