Arata Kato

Teurilene and thyrsiferyl 23-acetate, meso and remarkably cytotoxic compounds from the marine red alga laurencia obtusa (hudson) lamouroux

Abstract Two new cyclic ethers consisting of squalene carbon skeleton have been isolated from the red alga L. obtusa . The absolute stereostructure of teurilene ( 1 ) was elucidated by x-ray crystallographic method, and the structure of thyrsiferyl 23-acetate ( 2 ) was established from the spectral and chemical evidence.

Characterization of a Novel Human Tumor Necrosis Factor‐α Mutant with Increased Cytotoxic Activity

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.