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A novel tumor necrosis factor‐α mutant with significantly enhanced cytotoxicity and receptor binding affinity
Author(s) -
Shin NamKyu,
Lee Inkyoung,
Chang SeungGu,
Shin HangCheol
Publication year - 1998
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216549800202142
Subject(s) - mutant , tumor necrosis factor alpha , cytotoxicity , receptor , microbiology and biotechnology , wild type , cell culture , biology , mutation , chemistry , biochemistry , in vitro , gene , immunology , genetics
A novel tumor necrosis factor‐α mutant (mutant M3), in which Ser and Tyr at positions 52 and 56 were substituted by Ile and Phe, respectively, along with deletion of 7 N‐terminal amino acids, was prepared and its biological activities were investigated. The mutant exhibited a 14‐ to 24‐fold increase in the cytotoxicity relative to the wild‐type TNF on various cancer cell lines. The binding affinity of the mutant to TNF‐R55 and TNF‐R75 receptors was over 10‐fold higher than that of the wild‐type. TNF‐α and the mutant show similar CD spectra in the far‐UV region, indicating that the overall structure was not influenced by the mutations. The production of highly potent TNF‐α mutant utilizing increase of hydrophobicity in the region 52‐56 may provide a structural basis for a design of optimized TNF‐α as a therapeutic purpose.